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程序性坏死参与大鼠肠缺血再灌注所致肺损伤的发生 预览

Necroptosis Involves in Mechanism of Lung Injury Induced by Intestinal Ischemia- Reperfusion
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摘要 【目的】探讨程序性坏死是否参与肠缺血再灌注所致肺损伤的发病机制。【方法】雄性SD大鼠32只,随机分为4组(n=8):假手术组(sham组)、肠缺血再灌注组(I/R组)、程序性坏死特异性抑制剂Necrostatin-1组(Nec-1组)和溶剂二甲基亚砜组(DMSO组)。采用夹闭肠系膜上动脉1.5h再灌注6h的方法制备肠缺血再灌注损伤模型。sham组仅分离血管;Nec-1组及DMSO组分别于夹闭肠系膜上动脉前30min时腹腔注射Necrostatin.11.0mg/kg或等容量DMSO。于再灌注6h时取肺组织,测定肺含水率,HE染色后观察肺组织形态学并评分。采用Westernblot法和免疫组化法检测受体相互作用蛋白1(RIPl)和受体相互作用蛋白3(RIP3)的表达。【结果】与sham组相比,I/R组和DMSO组的肺组织形态学评分和肺含水率较高(P〈0.05),Nec-1组组织形态学评分和肺含水率较I/R组和DMSO组明显下降(P〈0.05),Nec-1组的肺组织含水率与sham组相比无统计学差异(P〉0.05)。Western—blot和免疫组化检测结果显示,I/R组和DMSO组的肺组织RIP1、RIP3的表达上调(P〈0.05),而Nec-1抑制RIPl及RIP3蛋白的表达(P〈0.05)。【结论】程序性坏死参与了大鼠肠缺血再灌注所致肺损伤,使用RIPl的特异性抑制剂Nec-1可以减轻肺损伤。 [ Objective] To explore whether neeroptosis is involved in the mechanism of lung injury induced by intestinal iseh- emia-reperfusion. [ Method ] Thirty-two healthy male Sprague-Dawley rats were randomly assigned into 4 groups (n = 8) : sham oper- ation group (sham group), ischemia/reperfusion group (I/R group), necroptosis inhibitor necrostatin- 1 group (Nec- 1 group) and solvent dimethyl sulfoxide (DMSO) group (DMSO group). Model of intestinal I/R injury was produced by clamping the superior rues- enteric artery for 1.5 h followed by 6 h reperfusion in rats. Necrostatin-1 1.0 mg/kg was administered 30 min before occlusion in Nec- 1 group, while the equal volume of DMSO was given instead in DMSO group. The rats were sacrificed at 6 h of reperfusion and the lung tissues were removed for measurement of wet-dry ratio and microscopic examination and scored. The expression of receptor-inter- acting protein 1 (RIP1) and receptor-interacting protein 3 (RIP3) in lung tissues was detected using Western-blot and immunohistochemistry. [ Result ] Compared with sham group, lung morphology score and wet/dry ratio in I/R, DMSO group raised (P 〈 0.05). Lung morphology score and wet/dry ratio statistically declined in Nec-1 group compared with I/R and DMSO group (P 〈 0.05) , while there was no statistical difference of wet/dry ratio between sham group and Nec-1 group (P 〉 0.05). As the result of westernblot and immunohistochemistry showed, the expression of RIP1 and RIP3 was up-regulated in I/R group and DMSO group (P 〈 0.05 ), which was inhibited by Nec-1 in Nec-1 group (P 〈 0.05 ). [ Conclusion ] Necroptosis is involved in the mechanism of lung injury induced by intestinal ischemia-reperfusion, and Nec-1, the special inhibitor of RIP1, can reduce the injury.
作者 杨芃 魏明 李响 温仕宏 刘克玄 YANG Peng1, WEI Ming1, LI Xiang1, WEN Shi-hong1, LIU Ke-xuan2 ( 1.Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; 2. Department of Anesthesiology, Nanfang Hospital of Southern Medical University, Guangzhou 510000, China)
出处 《中山大学学报:医学科学版》 CSCD 北大核心 2017年第3期321-326,共6页 Journal of Sun Yat-Sen University:Medical Sciences
基金 国家自然科学基金(81270456)
关键词 再灌注损伤 细胞死亡 intestine reperfusion injury lung cell death
作者简介 杨芃,博士研究生,主治医师,E-mail:ypsums@126.com; 刘克玄,通信作者,博士,教授,博士生导师,E-mail:liukexuan705@163.com.
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