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通窍活血汤对脑卒中大鼠肠道微生态紊乱所致炎症损伤的保护作用。

Protective Effect of Tong-Qiao-Huo-Xue Decoction on Inflammatory Injury Caused by Intestinal Microbial Disorders in Stroke Rats.

机构信息

Key Laboratory of Chinese Medicinal Formula of Anhui Province, Anhui University of Chinese Medicine.

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

出版信息

Biol Pharm Bull. 2020 May 1;43(5):788-800. doi: 10.1248/bpb.b19-00847. Epub 2020 Mar 3.

Abstract

Tong-Qiao-Huo-Xue Decoction (TQHXD) is a classic traditional Chinese medicine prescription for treating cerebral ischemia. The purpose of this study was to investigate the effect of TQHXD on intervening inflammatory response of ischemic stroke by regulating intestinal flora and repairing the intestinal barrier. A rat model of cerebral ischemia was established using middle cerebral artery occlusion (MCAO) and behavioral scores were performed. Additionally, the high throughput 16S ribosomal DNA (rDNA) sequence of intestinal bacteria in fecal samples of rat was also carried out. Our results showed that TQHXD could change the main components of intestinal flora in stroke rats, and reduced the excessive increase of Bacteroidetes, and also regulated the abnormal changes of abundance of some flora as well. In addition, the intestinal epithelial barrier was damaged after stroke, allowing bacterial metabolites to enter the blood, while TQHXD had an improved effect on this phenomenon. Meanwhile, pathological changes in the brain tissue and infarct volume were also alleviated by TQHXD. Due to the disorder of the intestinal flora and the destruction of the barrier, the peripheral immune imbalance caused an inflammatory reaction. TQHXD improved the imbalance of T cells, and inhibited the inflammatory response. Finally, the therapeutic transplantation of fecal microbiota also improved the outcome of stroke in rats. Our presented results suggest that TQHXD may improve the gut microbiota disorder and its induced inflammatory response after stroke, which could be a new target and mechanism for the treatment of stroke.

摘要

通窍活血汤是治疗缺血性脑卒中的经典中药方剂。本研究旨在探讨通窍活血汤通过调节肠道菌群和修复肠道屏障来干预缺血性脑卒中的炎症反应。采用大脑中动脉闭塞(MCAO)建立大鼠脑缺血模型,并进行行为评分。此外,还对大鼠粪便样本中的肠道细菌的高通量 16S 核糖体 DNA(rDNA)序列进行了分析。结果表明,通窍活血汤可改变脑卒中大鼠肠道菌群的主要成分,降低拟杆菌门的过度增加,并调节某些菌群丰度的异常变化。此外,脑卒中后肠道上皮屏障受损,使细菌代谢物进入血液,而通窍活血汤对此现象有改善作用。同时,脑组织的病理变化和梗死体积也通过通窍活血汤得到缓解。由于肠道菌群的紊乱和屏障的破坏,外周免疫失衡引起炎症反应。通窍活血汤改善了 T 细胞的失衡,并抑制了炎症反应。最后,粪便微生物群的治疗性移植也改善了大鼠脑卒中的预后。本研究结果表明,通窍活血汤可能改善脑卒中后肠道菌群紊乱及其诱导的炎症反应,这可能成为治疗脑卒中的新靶点和机制。

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