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补阳还五汤通过抑制 HIF-1α、VEGF 和促进β-ENaC 表达来预防大鼠缺血性脑卒中再灌注损伤。

Bu Yang Huan Wu decoction prevents reperfusion injury following ischemic stroke in rats via inhibition of HIF-1 α, VEGF and promotion β-ENaC expression.

机构信息

School of Traditional Chinese Medicine, Beijing Key Lab of TCM Collateral Disease Theory Research, Capital Medical University, Beijing, China.

Department of Gynecology, Dong Fang Hospital of Beijing University of Chinese Medicine, Beijing, China.

出版信息

J Ethnopharmacol. 2019 Jan 10;228:70-81. doi: 10.1016/j.jep.2018.09.017. Epub 2018 Sep 13.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Bu Yang Huan Wu Decoction (BYHW) is a famous traditional Chinese medicine (TCM) formula used in China for the treatment of cerebral ischemic stroke. But the protective effects and underlining mechanisms of BYHW remain unclear.

AIM OF THE STUDY

This study was designed to investigate the protective effects and underlining signaling mechanisms of BYHW on brain tissues in a rat model of cerebral ischemic reperfusion (I/R) injury.

MATERIALS AND METHODS

Liquid chromatography was used to verify the composition of BYHW. The cerebral edema and infarct volume were measured by magnetic resonance imaging (MRI). The morphology and ultrastructure of ischemic penumbra brain tissues were observed by hematoxylin-eosin (HE) and transmission electron microscopy (TEM). The expression levels of HIF-1 α, VEGF and β-ENaC were tested using immunohistochemistry technique, western blot and quantitative PCR analysis, respectively.

RESULTS

Administration of BYHW significantly decreased cerebral edema, rat neurological function scores, reduced brain infarct volume. At the same time, BYHW had protective effect on the blood-brain barrier (BBB), which improved the morphology and ultrastructure of ischemic penumbra brain tissues. BYHW treatment significantly decreased the protein and mRNA levels of HIF-1 α and VEGF compared with the model treatment. In addition, BYHW treatment significantly up-regulated the protein and mRNA levels of β-ENaC.

CONCLUSIONS

BYHW protected against cerebral I/R injury in MCAO rats through inhibiting the activation of the HIF-1 α /VEGF pathway and stabilizing ion channel of β-ENaC in brain, indicating that BYHW shows potential for stroke treatment in acute stage.

摘要

民族药理学相关性

补阳还五汤(BYHW)是一种在中国用于治疗脑缺血性中风的著名中药(TCM)配方。但 BYHW 的保护作用和潜在机制仍不清楚。

研究目的

本研究旨在探讨 BYHW 对脑缺血再灌注(I/R)损伤大鼠模型脑组织的保护作用及其潜在的信号机制。

材料与方法

采用液相色谱法验证 BYHW 的组成。采用磁共振成像(MRI)测量脑水肿和梗死体积。采用苏木精-伊红(HE)和透射电子显微镜(TEM)观察缺血半影区脑组织的形态和超微结构。采用免疫组织化学技术、western blot 和定量 PCR 分析分别检测 HIF-1α、VEGF 和β-ENaC 的表达水平。

结果

BYHW 给药可显著降低脑水肿、大鼠神经功能评分、减少脑梗死体积。同时,BYHW 对血脑屏障(BBB)有保护作用,改善了缺血半影区脑组织的形态和超微结构。与模型治疗相比,BYHW 治疗可显著降低 HIF-1α 和 VEGF 的蛋白和 mRNA 水平。此外,BYHW 治疗还可显著上调β-ENaC 的蛋白和 mRNA 水平。

结论

BYHW 通过抑制 HIF-1α/VEGF 通路的激活和稳定脑内β-ENaC 的离子通道,对 MCAO 大鼠的脑 I/R 损伤起到保护作用,表明 BYHW 在急性阶段具有治疗中风的潜力。

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