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羟基红花黄色素A调控Wnt/bβ-catenin通路保护脑缺血小鼠血脑屏障的机制研究

Study on the mechanism of the regulation of Wnt/β-catenin pathway by hydroxysafflor yellow A in the protection of blood brain barrier in cerebral ischemia mice
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摘要 目的 观察羟基红花黄色素A(hydroxysafflor yellow A, HSYA)对脑缺血模型小鼠血脑屏障的影响,探讨其作用机制。方法 将72只C57/BL小鼠按随机数字表法分为假手术组、TLR4阻断组、缺血模型组、TLR4阻断+缺血模型组、HSYA干预+缺血模型组、HSYA干预+TLR4阻断+缺血模型组。其中缺血模型组采用大脑中动脉栓塞法制备脑缺血模型,Toll样受体4(Toll-like receptor 4, TLR4)阻断采用右侧颈总动脉内注入10 μg/ml TLR4抗体0.1 ml进行干预,HSYA干预组于缺血前0.5 h尾静脉注射2 mg/kg HSYA溶液。采用RT-PCR、Western blot检测各组Wnt3a、b-catenin、Occludin和Claudin-5的mRNA和蛋白表达变化。结果 与缺血模型组比较,TLR4阻断+缺血模型组、HSYA干预+缺血模型组、HSYA干预+TLR4阻断+缺血模型组TLR4 mRNA[(1.63±0.05)、(1.53±0.04)、(1.84±0.03)比(1.97±0.05)]表达降低(P<0.05或P<0.01),Wnt3a mRNA [(0.56±0.01)、(0.58±0.01)、(0.50±0.04)比(0.42±0.03)]、b-catenin mRNA[(0.61±0.03)、(0.74±0.02)、(0.58±0.04)比(0.50±0.03)]、Claudin-5 mRNA [(0.54±0.02)、(0.58±0.01)、(0.47±0.01)比(0.46±0.02)]mRNA表达升高(P<0.05或P<0.01),TLR4蛋白[(1.73±0.05)、(1.57±0.03)、(1.79±0.08)比(1.89±0.02)]表达降低(P<0.05或P<0.01),Wnt3a蛋白[(0.67±0.03)、(0.74±0.03)、(0.57±0.01)比(0.46±0.01)]、Occludin蛋白[(0.66±0.02)、(0.73±0.02)、(0.67±0.01)比(0.53±0.01)]、Claudin-5蛋白[(0.71±0.01)、(0.73±0.01)、(0.66±0.01)比(0.64±0.03)]表达升高(P<0.05或P<0.01)。结论 TLR4对缺血小鼠脑组织中Wnt3a和b-catenin的活化起重要调控作用,HSYA可通过调控Wnt3a和β-catenin的表达对缺血脑组织紧密连接蛋白Occludin和Claudin-5进行干预,从而对缺血脑组织起到保护作用。 Objective To observe the effect of hydroxysafflor yellow A (HSYA) on the protection of blood brain barrier of cerebral ischemia mice, and explore the mechaniam. Methods Seventy-two C57/BL mice were divided into 6 groups: the sham operation group, the cerebral ischemia mice group, the TLR4 blocking group, the TLR4 blocking+cerebral ischemia mice group, the HSYA intervention+cerebral ischemia mice group, HSYA intervention+TLR4 blocking+cerebral ischemia mice group. Cerebral ischemia mice group were subjected to the middle cerebral artery occlusion (MCAO) model, TLR4 blocking was used, while TLR4 blocking was injected TLR4 antibody via right common carotid artery, and HSYA intervention group was injected 2 mg/kg HSYA by tail vein 0.5 h before cerebral ischemia. RT-PCR and western blot were applied to detect the mRNA and protein expression change of Wnt3a and β-catenin in each group. Results Compared with the cerebral ischemia mice group, the expression of TLR4 mRNA (1.63 ± 0.05, 1.53 ± 0.04, 1.84 ± 0.03 vs. 1.97 ± 0.05) significantly decreased (P〈0.05 or P〈0.01), the Wnt3a mRNA (0.56 ± 0.01, 0.58 ± 0.01, 0.50 ± 0.04 vs. 0.42 ± 0.03), b-catenin mRNA (0.61 ± 0.03, 0.74 ± 0.02, 0.58 ± 0.04 vs. 0.50 ± 0.03), Claudin-5 mRNA (0.54 ± 0.02, 0.58 ± 0.01, 0.47 ± 0.01 vs. 0.46 ± 0.02) mRNA significantly increased(P〈0.05 or P〈0.01), the protein expression of TLR4 (1.73 ± 0.05, 1.57 ± 0.03, 1.79 ± 0.08 vs. 1.89 ± 0.02) significantly decreased (P〈0.05 or P〈0.01), the protein expression of Wnt3a (0.67 ± 0.03, 0.74 ± 0.03, 0.57 ± 0.01 vs. 0.46 ± 0.01), Occludin (0.66 ± 0.02, 0.73 ± 0.02, 0.67 ± 0.01 vs. 0.53 ± 0.01), Claudin-5 (0.71 ± 0.01, 0.73 ± 0.01, 0.66 ± 0.01 vs. 0.64 ± 0.03) significantly increased (P〈0.05 or P〈0.01) in the TLR4 blocking+cerebral ischemia mice group, the HSYA intervention+cerebral ischemia mice group, HSYA intervention+TLR4 blocking+cerebral ischemia mice group. Conclusions TLR4 plays a
作者 付龙生 吕燕妮 徐彭 Fu Longsheng, Lyu Yanni, Xu Peng.(College of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China)
出处 《国际中医中药杂志》 2018年第3期226-230,共5页 International Journal of Traditional Chinese Medicine
基金 国家自然科学基金(8J760094) 江西省教育厅科学技术研究青年项目(GJJ160238) 江西省科技厅青年基金(20171BAB215021)
关键词 羟基红花黄色素A 脑缺血 血脑屏障 WNT蛋白质类 小鼠 Hydroxysafflower yellow A Brain ischemia Blood-brain barrier Wnt proteins Mice
作者简介 通信作者:吕燕妮,Email:lvyanni@126.com.
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