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通窍活血汤通过降低血脑屏障通透性对脑缺血损伤的保护作用

Protection of Tong-Qiao-Huo-Xue Decoction against Cerebral Ischemic Injury through Reduction Blood-Brain Barrier Permeability.

作者信息

Li Lili, Wang Ning, Jin Qizhong, Wu Qian, Liu Yafang, Wang Yan

机构信息

Key Laboratory of Xin'an Medicine, Ministry of Education.

Institute for Pharmacodynamics and Safety Evaluation of Chinese Medicine, Anhui Academy of Chinese Medicine.

出版信息

Chem Pharm Bull (Tokyo). 2017;65(11):1004-1010. doi: 10.1248/cpb.c17-00267.

DOI:10.1248/cpb.c17-00267
PMID:29093286
Abstract

Tong-Qiao-Huo-Xue Decoction (TQHXD) is a classical prescription in traditional Chinese medicine treating blood stagnation in the head and facial channels, especially cerebral ischemia. We investigate the effect of TQHXD on the expressions of related proteins of the blood-brain barrier (BBB) and analysis of constituents in the cerebrospinal fluid (CSF) on cerebral ischemic model rats. Here, we demonstrate that TQHXD protected the hippocampus neurons, reduced the opening of tight junction (TJ) and decreased the permeability of BBB by up-regulating ZO-1, occludin, claudin-5 expressions, down-regulating aquaporin-4 (AQP-4) and matrix metalloproteinase-9 (MMP-9) expressions. Meanwhile, we detected Muscone, ligustilide and hydroxysafflor yellow A in CSF on cerebral ischemic model rats. These compounds could be identified as the main active ingredients of TQHXD on protecting the damaged BBB. These results suggest that TQHXD could act as a potential neuroprotective agent against BBB damage for cerebral ischemia.

摘要

通窍活血汤是中医治疗头面经络血瘀,尤其是脑缺血的经典方剂。我们研究了通窍活血汤对脑缺血模型大鼠血脑屏障(BBB)相关蛋白表达的影响以及脑脊液(CSF)成分分析。在此,我们证明通窍活血汤通过上调紧密连接蛋白(ZO-1)、闭合蛋白、紧密连接蛋白-5的表达,下调水通道蛋白-4(AQP-4)和基质金属蛋白酶-9(MMP-9)的表达,保护海马神经元,减少紧密连接(TJ)的开放并降低血脑屏障的通透性。同时,我们在脑缺血模型大鼠的脑脊液中检测到麝香酮、川芎嗪和羟基红花黄色素A。这些化合物可被确定为通窍活血汤保护受损血脑屏障的主要活性成分。这些结果表明,通窍活血汤可能作为一种潜在的神经保护剂,对抗脑缺血引起的血脑屏障损伤。

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