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Silencing Huwe1 reduces apoptosis of cortical neurons exposed to oxygen-glucose deprivation and reperfusion 预览
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作者 Guo-Qian He Wen-Ming Xu +3 位作者 Hui-Juan Liao Chuan Jiang Chang-Qing Li Wei Zhang 《中国神经再生研究:英文版》 SCIE CAS CSCD 2019年第11期1977-1985,共9页
HECT, UBA and WWE domain-containing 1(Huwe1), an E3 ubiquitin ligase involved in the ubiquitin-proteasome system, is widely expressed in brain tissue. Huwe1 is involved in the turnover of numerous substrates, includin... HECT, UBA and WWE domain-containing 1(Huwe1), an E3 ubiquitin ligase involved in the ubiquitin-proteasome system, is widely expressed in brain tissue. Huwe1 is involved in the turnover of numerous substrates, including p53, Mcl-1, Cdc6 and N-myc, thereby playing a critical role in apoptosis and neurogenesis. However, the role of Huwe1 in brain ischemia and reperfusion injury remains unclear. Therefore, in this study, we investigated the role of Huwe1 in an in vitro model of ischemia and reperfusion injury. At 3 days in vitro, primary cortical neurons were transduced with a control or shRNA-Huwe1 lentiviral vector to silence expression of Huwe1. At 7 days in vitro, the cells were exposed to oxygen-glucose deprivation for 3 hours and reperfusion for 24 hours. To examine the role of the c-Jun N-terminal kinase(JNK)/p38 pathway, cortical neurons were pretreated with a JNK inhibitor(SP600125) or a p38 MAPK inhibitor(SB203508) for 30 minutes at 7 days in vitro, followed by ischemia and reperfusion. Neuronal apoptosis was assessed by TUNEL assay. Protein expression levels of JNK and p38 MAPK and of apoptosis-related proteins(p53, Gadd45 a, cleaved caspase-3, Bax and Bcl-2) were measured by western blot assay. Immunofluorescence labeling for cleaved caspase-3 was performed. We observed a significant increase in neuronal apoptosis and Huwe1 expression after ischemia and reperfusion. Treatment with the shRNA-Huwe1 lentiviral vector markedly decreased Huwe1 levels, and significantly decreased the number of TUNEL-positive cells after ischemia and reperfusion. The silencing vector also downregulated the pro-apoptotic proteins Bax and cleaved caspase-3, and upregulated the anti-apoptotic proteins Gadd45 a and Bcl-2. Silencing Huwe1 also significantly reduced p-JNK levels and increased p-p38 levels. Our findings show that downregulating Huwe1 affects the JNK and p38 MAPK signaling pathways as well as the expression of apoptosis-related genes to provide neuroprotection during ischemia and reperfusion. All animal experiments and 展开更多
关键词 nerve REGENERATION ischemic stroke oxygen-glucose DEPRIVATION and REPERFUSION ischemia/reperfusion cortical neuron ubiquitin proteasome system Huwe1 APOPTOSIS therapeutic targets CELL culture CELL death neural REGENERATION
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Uterine Reperfusion Ischemia and Use of Elastic Tourniquet 预览
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作者 J. F. Nnang Essone F. Ovono Abessolo +7 位作者 A. Tsagoulela G. Edjo Nkhilli P. Assoumou J. A. Bang Ntamack E. Anyunzok U. Minkobame J. F. Meye E. Ngou Milama 《生物科学与医学(英文)》 2019年第2期98-119,共22页
Introduction: In humans, it has not been established that the use of elastic tourniquet (ET) during myomectomies, whose delivery times do not exceed 90 minutes, which is responsible for ischemia reperfusion (I/R) syst... Introduction: In humans, it has not been established that the use of elastic tourniquet (ET) during myomectomies, whose delivery times do not exceed 90 minutes, which is responsible for ischemia reperfusion (I/R) systemic. Objectives: To study the plasma variations of markers of I/R during myomectomies performed with ET, whose exposure time does not exceed 90 minutes. Population and methods: Plasma créatinin phosphokinase kinase (CPK) and gluthatione peroxydase (GPX) levels of patients with ET myoma (M + G +, n = 19), taken before, during and after exposure, were compared to those of women operated on myoma without tourniquet (M + G -, n = 15), carriers of unoperated myomas (M + G0, n = 20) and controls (M0G0, n = 18). The duration of exposure of the ET was determined, and perioperative variations of GPX, Ca2+, K+ and CPK between M + G + and others groups were analyzed (p Results: The average duration of exposure of the ET was 51.56 ± 14.12 [30 - 88] min. In M + G +, prior to insertion, CPK was 71.64, GPX 3.537, Ca2+ 3.000, K+ 3.934, and did not vary from those of M + G - (CPK = 59.354, GPX = 3.205, Ca2+ = 2.525, K+ = 3.788), M + G0 (CPK = 71.640, GPX = 2.759, Ca2+ = 3.004, K+ = 3.934) and M0G0 (CPK = 57.2, GPX = 2.306, Ca2+ = 2.879, K+ = 3.705). Conversely, during the posture (CPK = 95.665, GPX = 3.645, Ca2+ = 3.642, K+ = 4.757) and after the release of the ET (CPK = 135.443, GPX = 3.694, Ca2+ = 3.892, K+ = 5.322), these rates were higher among the M + G + compared to the M + G0 and M0G0, but did not differ from those of the M + G - during (CPK = 91.270, GPX = 3.413, Ca2+ = 3.068, K+ = 4.257) and after release (CPK = 137.776, GPX = 3.632, Ca2+ = 3.148, K+ = 5.075). Conclusion: The plasmatic concentration of ischemia (CPK, K+) and reperfusion (GPX, Ca2+) biomarkers does not differ between M + G + and M + G -, but is elevated relatively to controls (M0G0), but also to M + G0’s group. These results show that, for exposure times not exceeding 90 minutes, the elastic tourniquet is probably not the cause of the in 展开更多
关键词 ISCHEMIA REPERFUSION UTERUS ELASTIC TOURNIQUET
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Temporal dynamics of immune response following prolonged myocardial ischemia/reperfusion with and without cyclosporine A
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作者 Vitali Rusinkevich Yin Huang +4 位作者 Zhong-yan Chen Wu Qiang Yi-gang Wang Yu-fang Shi Huang-tian Yang 《中国药理学报:英文版》 SCIE CAS CSCD 2019年第9期1168-1183,共16页
Understanding the dynamics of the immune response following late myocardial reperfusion is critical for the development of immunomodulatory therapy for myocardial infarction (MI). Cyclosporine A (CSA) possesses multip... Understanding the dynamics of the immune response following late myocardial reperfusion is critical for the development of immunomodulatory therapy for myocardial infarction (MI). Cyclosporine A (CSA) possesses multiple therapeutic applications for MI, but its effects on the inflammation caused by acute MI are not clear. This study aimed to determine the dynamics of the immune response following myocardial ischemia/reperfusion (I/R) and the effects of CSA in a mouse model of prolonged myocardial ischemia designated to represent the human condition of late reperfusion. Adult C57BL/6 mice were subjected to 90 min of closed-chest myocardial I/R, which induced severe myocardial injury and excessive infiammation in the heart. Multicomponent analysis of the immune response caused by prolonged I/R revealed that the peak of cytokines/chemokines in the systemic circulation was synchronized with the maximal infiux of neutrophils and T-cells in the heart 1 day after MI. The peak of cytokine/chemokine secretion in the infarcted heart coincided with the maximal macrophage and natural killer cell infiltration on day 3 after MI. The cellular composition of the mediastinal lymph nodes changed similarly to that of the infarcted hearts. CSA (10 mg/kg/day) given after prolonged I/R impaired heart function, enlarged the resulting scar, and reduced heart vascularization. It did not change the content of immune cells in hearts exposed to prolonged I/R, but the levels of MCP-1 and MIP-1α(hearts) and IL-12 (hearts and serum) were signi?cantly reduced in the CSA-treated group in comparison to the untreated group, indicating alterations in immune cell function. Our findings provide new knowledge necessary for the development of immunomodulatory therapy targeting the immune response after prolonged myocardial ischemia/reperfusion. 展开更多
关键词 myocardial INFARCTION ischemia REPERFUSION late REPERFUSION immune response inflammatory CYTOKINES angiogenesis CYCLOSPORINE A
依达拉奉联合阿替普酶对老年急性脑梗死患者再灌注的影响 预览
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作者 计悠扬 王一涵 +1 位作者 李畅畅 韩颖 《中国临床保健杂志》 CAS 2019年第2期233-236,共4页
目的探讨依达拉奉联合阿替普酶对老年急性脑梗死(ACI)患者再灌注的影响。方法选取老年ACI患者156例,采用随机数字表法将患者分为研究组(n=79)与对照组(n=77)。对照组采用阿替普酶治疗,研究组采用依达拉奉联合阿替普酶治疗,比较两组再灌... 目的探讨依达拉奉联合阿替普酶对老年急性脑梗死(ACI)患者再灌注的影响。方法选取老年ACI患者156例,采用随机数字表法将患者分为研究组(n=79)与对照组(n=77)。对照组采用阿替普酶治疗,研究组采用依达拉奉联合阿替普酶治疗,比较两组再灌注损伤、临床疗效、生化指标与药物安全性的差异。结果研究组治疗总有效率(92. 41%)明显高于对照组(68. 83%),(χ~2=13. 951,P <0. 001)。研究组再灌注损伤发生率(2. 53%)明显低于对照组(14. 29%),两组差异有统计学意义(χ~2=7. 052,P=0. 005)。治疗前,两组神经元特异性烯醇酶(NSE)、丙二醛(MDA)、超氧化物歧化酶(SOD)、超敏C反应蛋白(hs-CRP)、内皮素(ET)水平[(26. 31±4. 98)μg/L比(26. 28±5. 02)μg/L,(9. 65±1. 46) nmol/mL比(9. 71±1. 52) nmol/mL,(67. 95±14. 28) u/mL比(67. 85±15. 03) u/mL,(11. 26±1. 56)μmol/L比(11. 31±1. 63)μmol/L,(77. 69±9. 01) ng/L比(77. 71±8. 69) ng/L]比较,差异无统计学意义(t=0. 037,0. 251,0. 043,0. 196,0. 014;P=0. 971,0. 802,0. 966,0. 845,0. 989)。治疗后,两组SOD水平[(109. 68±20. 17) nmol/mL、(90. 25±14. 36) nmol/mL]明显高于治疗前,NSE、MDA、hs-CRP、ET水平明显低于治疗前(P均<0. 001),其中研究组SOD水平明显高于对照组,NSE、MDA、hs-CRP、ET水平明显低于对照组(P均<0. 001)。出院后持续随访3个月,研究组死亡率(0. 00%)明显低于对照组(15. 58%),χ~2=13. 338,P <0. 001。结论依达拉奉联合阿替普酶有助于明显降低老年ACI患者再灌注损伤,改善生化指标与预后状况,且药物安全性较高。 展开更多
关键词 脑梗死 再灌注 自由基清除剂 组织型纤溶酶原激活物 老年人
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老年大鼠大脑中动脉永久性缺血与缺血再灌注对大脑损伤的比较研究 预览
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作者 许娜 渠静 +6 位作者 王赛楠 江炜 奥婷 张君 张芹 肖淑英 张瑞华 《中国现代医学杂志》 CAS 2019年第16期17-21,共5页
目的探讨老年大鼠缺血再灌注对大脑的影响。方法将30只健康雄性老年(18~20月龄)SD大鼠随机分为假手术组(Sham组)、永久性缺血组(I组)及缺血再灌注组(I/R组),除Sham组外,其余两组采用线栓法复制老年大鼠大脑中动脉局灶缺血再灌注损伤模... 目的探讨老年大鼠缺血再灌注对大脑的影响。方法将30只健康雄性老年(18~20月龄)SD大鼠随机分为假手术组(Sham组)、永久性缺血组(I组)及缺血再灌注组(I/R组),除Sham组外,其余两组采用线栓法复制老年大鼠大脑中动脉局灶缺血再灌注损伤模型。术后24 h,2,3,5-氯化三苯基四氮唑检测大鼠脑梗死体积,ELISA法检测脑组织高迁移率族蛋白-1(HMGB1)和丙二醛(MDA)含量及超氧化物歧化酶(SOD)活性,Western blotting检测脑组织HMGB1的表达。结果与Sham组比较,I组脑梗死体积增加,SOD活性降低(P <0.05),MDA含量和HMGB1相对表达量升高(P <0.05)。与I组比较,I/R组大鼠脑梗死体积百分比减少,SOD活性上升(P<0.05),MDA含量和HMGB1相对表达量下降(P<0.05)。结论与永久性缺血相比,老年大鼠大脑中动脉缺血再灌注可减轻大脑损伤。 展开更多
关键词 脑缺血 再灌注 脑损伤
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重组人血小板活化因子乙酰水解酶对大鼠脑梗死后缺血半暗带神经细胞超微结构的影响 预览
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作者 徐玉玲 王启征 +5 位作者 黄蕾 曹裕民 高玉元 廖一夫 唐晓娜 张雄 《中华老年心脑血管病杂志》 CAS 北大核心 2019年第10期1080-1083,共4页
目的从超微结构探讨重组人血小板活化因子乙酰水解酶(recombinant platelet-activating factor acetylhydrolase,rPAF-AH)对脑梗死大鼠缺血半暗带神经元的影响。方法将90只SD大鼠随机分为rPAF-AH组、生理盐水组和假手术组,每组30只。建... 目的从超微结构探讨重组人血小板活化因子乙酰水解酶(recombinant platelet-activating factor acetylhydrolase,rPAF-AH)对脑梗死大鼠缺血半暗带神经元的影响。方法将90只SD大鼠随机分为rPAF-AH组、生理盐水组和假手术组,每组30只。建立大鼠右侧大脑中动脉栓塞再灌注模型,在第2、7、14天进行神经行为学评分及透射电镜观察神经元细胞形态学改变。结果与生理盐水组比较,rPAF-AH组大鼠在第7天[(1.62±0.74)分vs (2.14±0.73)分,P<0.05]、第14天[(1.29±0.46)分vs (1.71±0.64)分,P<0.05]神经行为学评分均明显下降。透射电镜下生理盐水组可见神经细胞水肿,周围间隙增宽,细胞变形,染色质凝集,随着时间延长,神经元细胞不可逆损伤而逐渐凋亡,核内染色质松散甚至完全溶解;rPAF-AH组初期可见神经细胞明显水肿,但随着治疗时间延长,神经元细胞结构基本完整,可逆性损伤可逐渐改善。结论 rPAF-AH能有效改善大鼠脑梗死后神经功能缺损,可能与其缺血半暗带神经细胞超微结构保护作用有关。 展开更多
关键词 血小板活化因子 1-烷基-2-乙酰甘油磷酸胆碱酯酶 脑梗死 再灌注 神经元
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Acupuncture preconditioning protects against myocardial ischemia/reperfusion injury mediated apoptosis through miR-214/NCX1 activation: a hypothesis 预览
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作者 Hai-Long Fan Yu-Lan Ren +1 位作者 Li-Zhen Yang Fei Wu 《TMR传统医学研究》 2019年第4期178-183,共6页
Early reperfusion of ischemic cardiac tissue is usually the best option to improve clinical outcome of angina pectoris, especially of acute myocardial infarction. However, myocardial reperfusion may cause an abnormal ... Early reperfusion of ischemic cardiac tissue is usually the best option to improve clinical outcome of angina pectoris, especially of acute myocardial infarction. However, myocardial reperfusion may cause an abnormal increase of intracellular Ca^2+-mediated cardiomyocyte death and consequent loss of cardiac function, which is referred to myocardial ischemia/reperfusion (I/R) injury. Recently, the microRNA-214 (miR-214)/Na^+/Ca^2+ exchanger (NCX) 1 co-expression is a key factor in cellular protection against myocardial apoptosis for myocardial I/R injury. Once activated, miR-214/NCX1 axis can inhibit several Ca^2+ downstream signaling effectors that mediate cell death simultaneously. Studies have shown that acupuncture preconditioning has a protective effect on myocardial I/R injury, but its mechanism deserves further research. It has been proved that acupuncture preconditioning for ischemic myocardium successfully inhibit multiple Ca2+ handling related microRNAs that mediate cell death pathways, and miR-214 is one of its targets. In terms of clinical practice, coronary heart disease (CHD) patients benefit a lot from this intervention. However, there is barely no study correlating acupuncture preconditioning to the miR-214/NCX1 co-expression in patients with CHD. This review aims to discuss whether there is some evidence to justify a recommendation of acupuncture preconditioning in CHD patients as a non-pharmacological therapeutic method to activate the miR-214/NCX1 co-expression network model. 展开更多
关键词 MiR-214/NCX1 Acupuncture PRECONDITIONING Coronary heart disease MYOCARDIAL ISCHEMIA REPERFUSION injury
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内皮素-1及其受体在缺血再灌注大鼠脑内的分布特征 预览
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作者 史颖 张健煜 +2 位作者 唐逸 张广慧 何明利 《医学研究生学报》 CAS 北大核心 2019年第7期700-704,共5页
目的内皮素-1(ET-1)有望成为治疗脑缺血性卒中的新靶点,且卒中后其血浆含量增多,但脑内变化情况尚不清楚。文章主要研究ET-1及其受体(ETR)在大鼠脑缺血卒中后各脑区的表达量和分布特征,以推断其与相关脑损伤的关系。方法将12只健康雄性S... 目的内皮素-1(ET-1)有望成为治疗脑缺血性卒中的新靶点,且卒中后其血浆含量增多,但脑内变化情况尚不清楚。文章主要研究ET-1及其受体(ETR)在大鼠脑缺血卒中后各脑区的表达量和分布特征,以推断其与相关脑损伤的关系。方法将12只健康雄性SD大鼠,随机数字表法分为假手术组和缺血再灌注组,每组6只。两组均建立大脑中动脉闭塞/再灌注模型,、但假手术组LICA不插入线栓。免疫组织化学法观测ET-1、ETR的脑区分布特征。结果缺血再灌注组梗死半球皮层中、尾壳核和海马中ET-1表达(0.230±0.019、0.198±0.008、0.183±0.002)较假手术组(0.107±0.005、0.110±0.028、0.101±0.005)明显升高(P<0.05);缺血再灌注组梗死半球脑室脉络丛、软脑膜血管、大脑中动脉血管中A型受体(ETRA)表达(0.131±0.001、0.132±0.005、0.121±0.008)较假手术组(0.086±0.009、0.063±0.003、0.079±0.003)明显升高(P<0.05);缺血再灌注组梗死半球皮层及海马中B型受体(ETRB)的表达(0.187±0.025、0.226±0.019)较假手术组(0.032±0.003、0.029±0.002)明显升高(P<0.05)。结论脑缺血再灌注后,脑内ET-1、ETR于各脑区内呈选择性表达,且其分布位点与缺血再灌注中受损的脑区可能相关。 展开更多
关键词 内皮素-1 受体 脑缺血 再灌注 时空表达
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急性缺血性脑卒中溶栓后出血性转化与灌注CT微血管通透性的相关性 预览
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作者 王玮娜 王志伟 +2 位作者 郑俊江 李静 姚海涛 《安徽医药》 CAS 2019年第12期2440-2443,共4页
目的探讨急性缺血性脑卒中病人溶栓后出血性转化发生情况及其与灌注CT微血管通透性的相关性。方法选取2014年1月至2016年12月在石家庄市第三医院诊断为急性缺血性脑卒中病人82例作为研究对象,采用回顾性分析法分析所有病人的临床资料,... 目的探讨急性缺血性脑卒中病人溶栓后出血性转化发生情况及其与灌注CT微血管通透性的相关性。方法选取2014年1月至2016年12月在石家庄市第三医院诊断为急性缺血性脑卒中病人82例作为研究对象,采用回顾性分析法分析所有病人的临床资料,按照资料中治疗后是否发生出血性转化分为未出血组43例和出血组39例。所有病人均行头颅CT检查,分析两组病人病侧灌注CT的主要参数,绘制受试者工作特征曲线(ROC),对灌注CT微血管通透性在急性缺血性脑卒中病人溶栓后出血性转化中的预测价值进行分析。结果①82例急性缺血性脑卒中病人溶栓后39例病人发生出血性转化,发生率为47.56%;②两组病人年龄、美国国立卫生研究院卒中量表(NIHSS)评分及大面积脑梗死比例比较差异有统计学意义(P<0.05);③出血组病人表面通透性(PS)(15.31±1.45)mL·min^-1·(100 g)^-1明显高于未出血组病人(10.14±3.61)mL·min^-1·(100 g)-1,且出血组病人脑血容量(CBV)和脑血流量(CBF)较未出血者明显较低,比较差异有统计学意义(P<0.05);④根据ROC曲线结果显示,PS在ROC曲线下的面积>0.9,诊断界值为5.86 mL·min^-1·(100 g)^-1,对急性缺血性脑卒中病人溶栓后出血性转化的预测价值灵敏度为94.72%,特异度为88.11%;⑤非条件因素logistic回归模型显示,年龄较大、NIHSS评分过高以及出现大面积梗死是导致急性缺血性脑卒中病人溶栓后出血性转化的独立危险因素(P<0.05)。结论灌注CT微血管通透性在急性缺血性脑卒中病人溶栓后出血性转化中的预测价值良好,当PS值大于5.86 mL·min^-1·(100 g)^-1时急性缺血性脑卒中病人溶栓后发生出血性转化的风险提高,能为临床静脉溶栓提供重要的参考依据。 展开更多
关键词 卒中 灌注成像 脑缺血 血栓溶解疗法/副作用 再灌注 脑出血 体层摄影术 螺旋计算机 毛细血管通透性 预测
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替格瑞洛对急性心肌梗死患者冠脉血流和短期预后的影响 预览
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作者 李其勇 苏莱 陶剑虹 《成都医学院学报》 CAS 2019年第2期187-192,共6页
目的评估急性ST段抬高型心肌梗死患者(STEMI)直接经皮冠状动脉介入治疗(PCI)术前早期负荷替格瑞洛对冠状动脉血流和短期预后的影响。方法选取急性ST段抬高型心肌梗死行直接PCI治疗的患者187例为研究对象,按照PCI术前负荷抗血小板药物不... 目的评估急性ST段抬高型心肌梗死患者(STEMI)直接经皮冠状动脉介入治疗(PCI)术前早期负荷替格瑞洛对冠状动脉血流和短期预后的影响。方法选取急性ST段抬高型心肌梗死行直接PCI治疗的患者187例为研究对象,按照PCI术前负荷抗血小板药物不同分为替格瑞洛组(T组)和氯吡格雷组(C组),每组再根据患者总缺血时间中位数分为T1组(<180min)、T2组(≥180min);C1组(<180min)和C2组(≥180min),比较各组冠脉TIMIⅢ级血流患者比例、PCI术后2h内心电图ST段完全回落(STR50%)、术后校正的TIMI血流计数帧数(CTFC)及对心功能的影响;短期随访3个月评估其安全性。结果与T1、C1组比较,T2、C2组在PCI术后STR50%较低,CTFC较高,差异有统计学意义(P<0.05);与T1和T2组比较,C1和C2组在PCI术后STR50%较低,CTFC较高,差异有统计学意义(P<0.05)。出院后3个月随访时T组左心室射血分数(LVEF)高于C组(P=0.027);MACE事件和再发心绞痛低于C组,差异有统计学意义(P<0.05)。结论STEMI患者行直接PCI术前早期替格瑞洛可带来更好的STR50%和CTFC改善,短期随访显示可改善心功能和预后而不增加出血风险,疗效及安全性良好。 展开更多
关键词 急性心肌梗死 抗血小板药物 再灌注 短期预后
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Combined bone marrow stromal cells and oxiracetam treatments ameliorates acute cerebral ischemia/reperfusion injury through TRPC6
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作者 Jing Wang Ruohan Sun +1 位作者 Zhenzhu Li Yujun Pan 《生物化学与生物物理学报:英文版》 SCIE CAS CSCD 2019年第8期767-777,共11页
Ischemic stroke has become one of the leading causes of deaths and disabilities all over the world.In this study,we investigated the therapeutic effects of combined bone marrow stromal cells(BMSCs)and oxiracetam treat... Ischemic stroke has become one of the leading causes of deaths and disabilities all over the world.In this study,we investigated the therapeutic effects of combined bone marrow stromal cells(BMSCs)and oxiracetam treatments on acute cerebral ischemia/reperfusion(I/R)injury.A rat model of middle cerebral artery occlusion(MCAO)followed by complete reperfusion,as well as a cortex neuron oxygen-glucose deprivation(OGD)model was established.When compared with BMSCs or oxiracetam monotherapy,combination therapy significantly improved functional restoration with decreased infarct volume in observed ischemic brain.We propose that it may occur through the transient receptor potential canonical(TRPC)6 neuron survival pathway.The increased expression of TRPC6 along with the reduction of neuronal cell death in the OGD cortex neurons and combination therapy group indicated that the TRPC6 neuron survival pathway plays an important role in the combined BMSCs and oxiracetam treatments.We further tested the activity of the calpain proteolytic system,and the results suggested that oxiracetam could protect the integrity of TRPC6 neuron survival pathway by inhibiting TRPC6 degradation.The protein levels of phospho-cAMP response element binding protein(p-CREB)were tested.It was found that BMSCs play a role in the activation of the TRPC6 pathway.Our study suggests that the TRPC6 neuron survival pathway plays a significant role in the protective effect of combined BMSCs and oxiracetam treatments on acute cerebral I/R injury.Combined therapy could inhibit the abnormal degradation of TRPC6 via decreasing the activity of calpain and increasing the activation of TRPC6 neuron survival pathway. 展开更多
关键词 cerebral ischemia REPERFUSION NEUROPROTECTIVE therapy BMSCs OXIRACETAM TRPC6
Inhibition of FOXO3a/BIM signaling pathway contributes to the protective effect of salvianolic acid A against cerebral ischemia/reperfusion injury
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作者 Junke Song Wen Zhang +5 位作者 Jinhua Wang Haiguang Yang Qimeng Zhou Haigang Wang Li Li Guanhua Du 《药学学报:英文版》 CSCD 2019年第3期505-515,共11页
Salvianolic acid A(SalA) is an effective compound extracted from traditional Chinese medicine Salvia miltiorrhiza Bunge. The Forkhead box O3a(FOXO3a) signaling pathway plays crucial roles in the modulation of ischemia... Salvianolic acid A(SalA) is an effective compound extracted from traditional Chinese medicine Salvia miltiorrhiza Bunge. The Forkhead box O3a(FOXO3a) signaling pathway plays crucial roles in the modulation of ischemia-induced cell apoptosis. However, no information about the regulatory effect of SalA on FoxO3a is available. To explore the anti-cerebral ischemia effect and clarify the therapeutic mechanism of SalA, SH-SY5Y cells and Sprague–Dawley rats were applied, which were exposed to oxygen glucose deprivation/reoxygenation(OGD/R) and middle cerebral artery occlusion/reperfusion(MCAO/R) injuries, respectively. The involved pathway was identified using the specific inhibitor LY294002. Results showed that SalA concentration-dependently inhibited OGD/R injury triggered cell viability loss. SalA reduced cerebral infarction, lowered brain edema, improved neurological function, and inhibited neuron apoptosis in MCAO/R rats, which were attenuated by the treatment of phosphatidylinositol-4,5-bisphosphate 3-kinase(PI3K) specific inhibitor LY294002. SalA time-and concentration-dependently upregulated the phosphorylation levels of protein kinase B(AKT) and its downstream protein FOXO3a. Moreover, the nuclear translocation of FOXO3a was inhibited by SalA both in vivo and in vitro, which was also reversed by LY294002. The above results indicated that SalA fought against ischemia/reperfusion damage at least partially via the AKT/FOXO3a/BIM pathway. 展开更多
关键词 Salvianolic acid A ISCHEMIA REPERFUSION FOXO3A BIM NEUROPROTECTION
强化极化液对急性心肌梗死病人介入治疗后心肌再灌注及炎性因子的影响 预览
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作者 董国良 《中西医结合心脑血管病杂志》 2019年第12期1781-1784,共4页
目的探讨强化极化液对急性心肌梗死病人介入治疗后心肌再灌注及炎性因子的影响。方法选取2015年5月-2017年5月于我院行急诊经皮冠状动脉介入(PCI)治疗的急性ST段抬高型心肌梗死病人116例,随机分为观察组和对照组,各58例。对照组给予常... 目的探讨强化极化液对急性心肌梗死病人介入治疗后心肌再灌注及炎性因子的影响。方法选取2015年5月-2017年5月于我院行急诊经皮冠状动脉介入(PCI)治疗的急性ST段抬高型心肌梗死病人116例,随机分为观察组和对照组,各58例。对照组给予常规治疗联合0.9%氯化钠注射液,观察组在常规治疗基础上联合强化极化液治疗。比较两组心肌梗死溶栓治疗(TIMI)分级、再灌注心律失常发生率、心电图ST段回落率(STR),检测并比较两组术前和术后24h、3d、7d、10d超敏C反应蛋白(hs-CRP)、B型脑钠肽(BNP)、细胞可溶性凋亡相关因子(s-FAS)水平。结果观察组TIMI分级和再灌注窦性心动过缓、再灌注室性心动过速、再灌注房室传导阻滞发生率显著优于对照组,差异有统计学意义(P<0.05)。术后24h、3d、7d、10d,观察组s-FAS、hs-CRP、BNP水平显著低于对照组,差异有统计学意义(P<0.05)。结论强化极化液可降低急性心肌梗死病人介入治疗后血清s-FAS、hs-CRP、BNP水平,减轻心肌再灌注损伤。 展开更多
关键词 急性心肌梗死 强化极化液 经皮冠状动脉介入 再灌注 超敏C反应蛋白 B型脑钠肽 细胞可溶性凋亡相关因子
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急性ST段抬高型心肌梗死患者再灌注治疗预后的影响因素 预览 被引量:1
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作者 兰谋 彭源源 尹娟 《西部医学》 2019年第3期383-387,共5页
目的探讨急性ST段抬高型心肌梗死(STEMI)患者再灌注治疗预后的影响因素。方法选取2012年1月~2015年1月于我院行再灌注治疗的126例STEMI患者作为研究对象,采用回顾性分析所有患者的临床及随访资料,根据其资料结果记录所有患者的性别、年... 目的探讨急性ST段抬高型心肌梗死(STEMI)患者再灌注治疗预后的影响因素。方法选取2012年1月~2015年1月于我院行再灌注治疗的126例STEMI患者作为研究对象,采用回顾性分析所有患者的临床及随访资料,根据其资料结果记录所有患者的性别、年龄、疾病史等一般临床资料,疾病情况、血红蛋白等相关临床指标水平以及再灌注治疗后的预后效果,并比较不同预后效果患者间上述资料的差异性。分析影响再灌注治疗STEMI患者预后的因素。结果126例STEMI患者经再灌注治疗后预后好106例(84.13%),预后差20例(15.87%);年龄≥60岁的STEMI患者其女性和糖尿病比例以及心功能killip分级较高,而吸烟和饮酒患者较少,血红蛋白水平较低,预后较差(P<0.05);中、重度贫血患者其女性、吸烟、糖尿病比例和年龄及心功能能killip分级均高于非贫血和轻度贫血者,且前两者预后更差比较差异间均具有统计学意义(P<0.05);既往存在糖尿病病史,有吸烟、喝酒习惯,心功能killip分级过高、血脂异常以及年龄≥60岁和中、重度贫血的STEMI患者经再灌注治疗后其预后较差(P<0.05);经非条件多因素Lgistic回归模型分析显示,killip分级过高、血脂异常以及年龄≥60岁和中、重度贫血是影响STEMI再灌注治疗预后效果的独立危险因素(P<0.05)。结论STEMI患者经再灌注治疗后的预后效果尚可,年龄≥60岁和中、重度贫血等均为影响STEMI再灌注治疗预后效果的独立危险因素,可将其联合作为临床上评估STEMI患者经再灌注治疗预后效果的有效指标。 展开更多
关键词 年龄 血红蛋白 急性ST段抬高型心肌梗死 再灌注 预后影响
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心肌梗死再灌注早期磁共振心肌应变的初步研究 被引量:1
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作者 夏睿 朱桐 +6 位作者 张钰 陈榆舒 王磊 廖继春 李咏梅 吕发金 郜发宝 《四川大学学报:医学版》 CAS CSCD 北大核心 2019年第4期489-493,共5页
目的应用磁共振成像(MRI)心肌应变技术研究心肌梗死患者经皮冠状动脉介入治疗(PCI)后及心肌梗死再灌注模型大鼠不同节段的心肌应变特点。方法 10例心肌梗死患者在PCI术后早期(2~10 d)进行MRI检查,完成序列扫描后,经患者肘正中静脉注入... 目的应用磁共振成像(MRI)心肌应变技术研究心肌梗死患者经皮冠状动脉介入治疗(PCI)后及心肌梗死再灌注模型大鼠不同节段的心肌应变特点。方法 10例心肌梗死患者在PCI术后早期(2~10 d)进行MRI检查,完成序列扫描后,经患者肘正中静脉注入磁共振对比剂[按0.1 mmol/kg体质量注入钆喷酸葡胺(Gd-DTPA)],10 min后采集对比剂延迟增强图像(LGE),测量心内膜心肌应变运动参数,包括径向应变(RS)、周向应变(CS)峰值,在每一层心肌选取完全心肌梗死、部分心肌梗死及无梗死3个节段进行统计学分析。10只SD大鼠行冠状动脉左前降支结扎60 min后松开制备心肌梗死再灌注模型,在再灌注48 h及7 d采集MRI数据,分别勾画并计算:收缩末期及舒张末期心肌梗死面积所占整体心肌比例、舒张末期容积(EDV)、射血分数(EF)。心肌应变分析方法与患者类似。结果心肌梗死患者的RS和CS在完全心肌梗死节段及部分心肌梗死节段均小于无梗死心肌节段(P均<0.01),但完全心肌梗死节段与部分心肌梗死节段间差异无统计学意义(P>0.05)。大鼠再灌注48 h与7 d的EF及EDV差异无统计学意义(P>0.05);完全心肌梗死节段及部分心肌梗死节段的RS、 CS均小于无梗死心肌节段(P均<0.01),完全心肌梗死节段与部分心肌梗死节段间差异无统计学意义(P>0.05)。再灌注48 h心肌整体应变(RS和CS)与7 d相比变化不大(P>0.05),但48 h完全心肌梗死节段、部分心肌梗死节段及无梗死心肌节段心肌应变峰值小于7 d(P<0.05)。结论心肌梗死再灌注早期完全梗死节段及部分梗死节段心肌应变峰值没有差异。再灌注损伤会导致心肌梗死再灌注早期心肌运动能力降低,但随着再灌注时间延长,心肌运动能力逐渐恢复。 展开更多
关键词 心肌梗死 再灌注 磁共振 心肌应变
Garlicin Post-conditioning Suppresses Adhesion Molecules in Porcine Model of Myocardial Ischemia-Reperfusion Injury
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作者 YANG Peng LI Jia-hui +4 位作者 LI Ai-li LI Jing WANG Yong REN Shi-yan LI Xian-lun 《中国结合医学杂志:英文版》 SCIE CAS CSCD 2019年第1期31-36,共6页
Objective: To evaluate whether garlicin post-conditioning can attenuate myocardial ischemiareperfusion injury in a catheter-based porcine model of acute myocardial infarction(AMI) by affecting adhesion molecules integ... Objective: To evaluate whether garlicin post-conditioning can attenuate myocardial ischemiareperfusion injury in a catheter-based porcine model of acute myocardial infarction(AMI) by affecting adhesion molecules integrin β1/CD29 and platelet endothelial cell adhesion molecule-1(PECAM-1/CD31). Methods: Twenty-two swine were devided into 3 groups: 6 in a sham-operation group, and 8 each in the model and garlicin groups. AMI porcine model was established in the model and garlicin groups. The distal parts of the left anterior descending coronary artery in the animals of the model and garlicin groups were occluded by dilated balloon for 2 h, followed by reperfusion for 3 h. Garlicin(1.88 mg/kg) was injected over a period of 1 h, beginning just before reperfusion, in the garlicin group. Real-time polymerase chain reaction, immunohistochemistry and Western blot were carried out to detect mRNA and protein expressions of CD29 and CD31 3 h after reperfusion. Results: Hematoxylin-eosin staining showed a better myocardial structure in the garlicin group after reperfusion. Compared to the model group, garlicin inhibited both the mRNA and protein expression of CD29 and CD31 in reperfusion area and no-reflow area(both P<0.05). Conclusions: Garlicin post-conditioning induced cardio-protection against myocardial ischemia-reperfusion injury in this catheter-based porcine model of AMI. The cardio-protective effect of garlicin is possibly owing to suppression of production of CD29 and CD31, by inhibition of the m RNA expression of CD29 and CD31. 展开更多
关键词 garlicin REPERFUSION injury myocardial INFARCTION CD29 CD31
枳实薤白桂枝汤对心肌缺氧家兔左心室内压的影响 预览
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作者 赵楠 贾洪涛 +1 位作者 冯月男 孙世晓 《河北中医》 2019年第6期905-909,926共6页
目的观察枳实薤白桂枝汤对心肌缺氧家兔左心室内压的影响,探讨其机制。方法将50只正常成年家兔按照随机数字表法分为正常组、模型组及枳实薤白桂枝汤高、中、低剂量组,每组10只。各组家兔手术活体取心,应用离体心脏灌流系统制备洛克氏... 目的观察枳实薤白桂枝汤对心肌缺氧家兔左心室内压的影响,探讨其机制。方法将50只正常成年家兔按照随机数字表法分为正常组、模型组及枳实薤白桂枝汤高、中、低剂量组,每组10只。各组家兔手术活体取心,应用离体心脏灌流系统制备洛克氏液心脏灌流模型,其中正常组灌注含饱和氧的洛克氏液,模型组予不含氧的洛克氏液灌注,枳实薤白桂枝汤高、中、低剂量组予不含氧的洛克氏液+相应剂量(1.58、0.79、0.395g/kg)的枳实薤白桂枝汤提取液灌注。记录灌注前和灌注20min后各时间点左心室收缩压(LVSP)、左心室舒张末压(LVEDP)、左室内压等容相最大上升速率(+dp/dtmax)及左室内压等容相最大下降速率(-dp/dtmax)的变化。结果与正常组比较,模型组在灌注后5~30min各时间点LVSP、+dp/dtmax、-dp/dtmax均降低(P<0.01),LVEDP升高(P<0.01)。与模型组比较,枳实薤白桂枝汤低剂量组LVEDP在灌注后5、10min时间点均降低(P<0.01),LVSP在灌注后5、10、15min时间点均升高(P<0.01),+dp/dtmax、-dp/dtmax在灌注后5、10min时间点均升高(P<0.01);枳实薤白桂枝汤中剂量组LVEDP在灌注后5~25min各时间点均降低(P<0.01,P<0.05),LVSP、+dp/dtmax、-dp/dtmax在灌注后5~30min各时间点均升高(P<0.01,P<0.05);枳实薤白桂枝汤高剂量组LVEDP在灌注后5、10min时间点均降低(P<0.01),LVSP、+dp/dtmax、-dp/dtmax在灌注后5、10min时间点均升高(P<0.01)。与枳实薤白桂枝汤低剂量组比较,枳实薤白桂枝汤中剂量组LVEDP在灌注后10~25min各时间点均降低(P<0.05);LVSP在灌注后5~30min各时间点均升高(P<0.05);+dp/dtmax在灌注后10~30min各时间点均升高(P<0.05);-dp/dtmax在灌注后15~25min各时间点均升高(P<0.05)。结论枳实薤白桂枝汤中剂量组对缺氧心脏泵血功能障碍有显著改善作用。 展开更多
关键词 枳实薤白桂枝汤 冠心病 低氧 再灌注 模型 动物 心室功能 动物实验
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Phloroglucinol,a nutraceutical for IR‐induced cardiac damage in diabetic rats 预览
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作者 B.Pranav Nayak K.R.Ganesha +2 位作者 Nathani Minaz Rema Razdan Sumanta Kumar Goswami 《动物模型与实验医学(英文)》 CSCD 2019年第3期210-216,共7页
Background:Myocardial injury due to ischemia‐reperfusion(IR)is aggravated in diabetes which is associated with oxidative stress.Alleviating oxidative stress via use of antioxidants has been shown to be effective at m... Background:Myocardial injury due to ischemia‐reperfusion(IR)is aggravated in diabetes which is associated with oxidative stress.Alleviating oxidative stress via use of antioxidants has been shown to be effective at minimizing myocardial cell death and improving cardiac function.The aim of the present study was to evaluate the cardioprotective effect of phloroglucinol against myocardial reperfusion injury(MRI)in diabetic rats.Methods:Diabetes was induced in female rats with streptozotocin(50 mg/kg).The diabetic rats were orally treated with phloroglucinol(100 and 200 mg/kg daily for 28 days).After treatment the hearts were isolated and mounted on a Langendorff apparatus.The hearts were subjected to 15 minutes of IR to induce myocardial damage.Cardiac functions including heart rate(HR),resting and developed tension,and rate of change of contraction(+dP/dtmax)were recorded.Cardiac injury biomarkers lactate dehydrogenase(LDH)and creatine kinase(CK‐MB)were measured in the heart perfusate.Levels of the antioxidant enzymes reduced glutathione(GSH)and malondialdehyde(MDA)were measured.Hematoxylin and eosin(H&E)staining was also performed.Results:After IR injury,a decrease in HR and+dP/dtmax in hearts from diabetic rat was seen compared to healthy rat hearts,which was reversed by phloroglucinol treatment.Myocardial infarct size,measured by H&E staining,was increased in diabetic rats compared to healthy rats and an increase in the activity of LDH and CK‐MB in the heart perfusate in diabetic rats was decreased by phloroglucinol treatment.An increase in MDA levels and a decrease in levels of antioxidant enzymes were observed in diabetic rats,which was reversed with phloroglucinol treatment.Conclusion:Phloroglucinol treatment has potential therapeutic promise in the treatment of MRI in diabetes. 展开更多
关键词 Langendroff apparatus MYOCARDIAL REPERFUSION INJURY PHLOROGLUCINOL STREPTOZOTOCIN
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大鼠脑缺血再灌注后大脑皮质小胶质细胞活化及炎症因子的表达
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作者 程曼 杨柳 +2 位作者 王梦影 梁晓珊 张绪梅 《军事医学》 CAS 北大核心 2019年第2期126-132,共7页
目的检测大鼠缺血再灌注(I/R)后不同时间点大脑皮质小胶质细胞活化情况,同时探究小胶质细胞中的炎症因子白细胞介素6(IL-6)、IL-1β和肿瘤坏死因子α(TNF-α)的表达变化规律。方法通过线栓法制备SD大鼠大脑中动脉栓塞(MCAO)的脑缺血再... 目的检测大鼠缺血再灌注(I/R)后不同时间点大脑皮质小胶质细胞活化情况,同时探究小胶质细胞中的炎症因子白细胞介素6(IL-6)、IL-1β和肿瘤坏死因子α(TNF-α)的表达变化规律。方法通过线栓法制备SD大鼠大脑中动脉栓塞(MCAO)的脑缺血再灌注模型,实验动物随机分为假手术组(SHAM组)、MCAO再灌3 h组(MCAO 3 h组)、MCAO 6 h组、MCAO 12 h组、MCAO 18 h组、MCAO 24 h组和MCAO 72 h组。苏木精-伊红(HE)染色法检测大鼠大脑皮质神经细胞形态改变。Western印迹检测各组大鼠大脑皮质Iba-1的表达。免疫荧光双标记法检测小胶质细胞中炎症因子IL-6、IL-1β和TNF-α的表达水平。结果与SHAM组比较,MCAO各组大鼠皮质的神经细胞损伤严重,Iba-1蛋白表达显著升高(P<0.05)。除IL-1β的表达在MCAO术后3 h与SHAM组比较无显著差异外,其他各MCAO组炎症因子IL-1β、IL-6和TNF-α在小胶质细胞中的表达均显著提高(P<0.05)。此外,3种炎症因子的表达均在MCAO术后24 h达到高峰后开始下降,与MCAO 72 h组相比,差异有统计学意义(P<0.05)。结论 I/R可导致大鼠患侧皮质神经细胞的损伤和小胶质细胞的激活,并导致激活的小胶质细胞中的炎症因子释放增加,且表达高峰存在一致性。 展开更多
关键词 脑缺血 再灌注 小神经胶质细胞 白细胞介素6 白细胞介素1Β 肿瘤坏死因子α
PCI术前应用单硝酸异山梨酯注射液治疗ST段抬高型心肌梗死再灌注后早期心律失常的疗效 预览
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作者 周芃 陈丰毅 孙运 《中国合理用药探索》 CAS 2019年第1期93-97,共5页
目的:探讨经皮冠状动脉介入治疗术(PCI)术前应用单硝酸异山梨酯注射液治疗ST段抬高型心肌梗死(STEMI)再灌注后早期心律失常的疗效及对超声心动图、心肌酶谱的影响.方法:选取2014年6月—2017年6月于我院行PCI治疗的176例STEMI患者为研究... 目的:探讨经皮冠状动脉介入治疗术(PCI)术前应用单硝酸异山梨酯注射液治疗ST段抬高型心肌梗死(STEMI)再灌注后早期心律失常的疗效及对超声心动图、心肌酶谱的影响.方法:选取2014年6月—2017年6月于我院行PCI治疗的176例STEMI患者为研究对象,按照随机数字表法分为观察组与对照组,各88例.对照组给予常规术前药物治疗,观察组在对照组基础上于术前注射单硝酸异山梨酯注射液(150μg/kg,术前30 min时静脉推注).比较术后2 h及术后24 h时,两组心肌酶谱[肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)]、肌钙蛋白[肌钙蛋白T(TnT)、肌钙蛋白I(TnI)]水平变化,分析术后24 h内心电图ST段回落幅度、心律失常发生情况、术后1个月时超声心动图指标[左室射血分数(LVEF)、左室收缩末期直径(LVESd)、左室舒张末期直径(LVEDd)]及1个月内心血管不良事件发生情况.结果:术后24 h时,两组血浆CK-MB、LDH水平均较术后2 h时显著下降,且观察组明显低于同期对照组,差异有统计学意义(P<0.05);术后24 h时,两组血浆TnT、TnI水平均较术后2 h时显著下降,且观察组明显低于同期对照组,差异有统计学意义(P<0.05);术后24 h内,观察组心电图ST段回落幅度明显大于对照组(P<0.05);术后24 h内,观察组各类心律失常发生率均明显低于对照组,差异有统计学意义(P<0.05);术后1个月时,观察组LVEF水平明显高于对照组,LVESd、LVEDd水平明显低于对照组,差异有统计学意义(P<0.05);两组各项心血管不良事件发生率比较,差异无统计学意义(P>0.05).结论:STEMI患者PCI术前注射单硝酸异山梨酯可有效避免术后早期再灌注性心律失常的出现,降低超声心动图指标及心肌酶谱水平,减轻心肌损伤,改善心功能,有利于患者预后恢复. 展开更多
关键词 经皮冠状动脉介入治疗术 单硝酸异山梨酯注射液 ST段抬高心肌梗死 再灌注 心律失常
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