中国神经再生研究(英文版) ›› 2017, Vol. 12 ›› Issue (3): 425-432.doi: 10.4103/1673-5374.202946

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

中药发酵液栓通灵减轻缺血性脑卒中作用途径:抑制炎症和细胞凋亡

  

  • 收稿日期:2017-02-07 出版日期:2017-03-15 发布日期:2017-03-15
  • 基金资助:

    中国国家自然科学基金项目(81202625);三峡大学缺血性心脑疾病转化医学重点实验室开放基金课题(2016xnxg101

Fermented Chinese formula Shuan-Tong-Ling attenuates ischemic stroke by inhibiting inflammation and apoptosis

Zhi-gang Mei1, 2, Ling-jing Tan1, 2, Jin-feng Wang1, Xiao-li Li1, Wei-feng Huang1, Hua-jun Zhou3   

  1. 1 Third-Grade Pharmacological Laboratory on Chinese Medicine Approved by State Administration of Traditional Chinese Medicine, Medical College of China Three Gorges University, Yichang, Hubei Province, China; 2 Key Laboratory of Cardiovascular and Cerebrovascular Diseases Translational Medicine, China Three Gorges University, Yichang, Hubei Province, China; 3 Institute of Neurology, the First College of Clinical Medical Sciences, China Three Gorges University, Yichang, Hubei Province, China
  • Received:2017-02-07 Online:2017-03-15 Published:2017-03-15
  • Contact: Zhi-gang Mei, M.D.,zhigangmei@139.com.
  • Supported by:

    This study was supported by the National Natural Science Foundation of China, No. 81202625; and Open Fund of Key Laboratory of Cardiovascular and Cerebrovascular Diseases Translational Medicine of China Three Gorges University of China, No. 2016xnxg101.

摘要:

中药发酵液栓通灵由葛根、丹参、姜黄、山楂、石见穿、白芥子、黄芪、竹节参、白术、白芍、柴胡、菊花、香附和天麻共14味中药的水提液经酵母菌、乳酸菌和醋酸菌等益生菌发酵而成,在临床上用于治疗缺血性卒中、偏头痛、血管性痴呆等脑部疾病。作者既往研究表明,栓通灵可以减轻H2O2诱导的大鼠大脑微血管内皮细胞的氧化应激损伤,但其机制尚不清楚。为此,本组实验设计为大鼠大脑中动脉闭塞前连续7d灌胃5.7,17.2mL/kg栓通灵,结果显示栓通灵可以缩小缺血性脑卒中大鼠脑梗死体积,增加神经功能评分,降低缺血侧海马组织中肿瘤坏死因子α和白细胞介素1β的水平,并上调沉默信息调节因子1及Bcl-2水平下调乙酰化p53和Bax水平;同时蛛网膜下腔注射5 mg/kg沉默信息调节因子1特异性抑制剂EX527,每2d一次,连续4次,则出现逆转上述变化的现象。说明栓通灵是通过活化沉默信息调节因子1信号通路而减轻缺血性脑卒中损伤导致的炎症反应和细胞凋亡。

ORCID:0000-0002-0377-7785(Zhi-gang Mei)

关键词: 神经再生, 中医, 发酵, 栓通灵, 大脑中动脉闭塞, 脑缺血再灌注, 沉默信息调节因子1, 炎症, 细胞凋亡, 肿瘤坏死因子α, 白细胞介素1β, Bcl-2, Bax, 乙酰化p53

Abstract:

The fermented Chinese formula Shuan-Tong-Ling is composed of radix puerariae (Gegen), salvia miltiorrhiza (Danshen), radix curcuma (Jianghuang), hawthorn (Shanzha), salvia chinensis (Shijianchuan), sinapis alba (Baijiezi), astragalus (Huangqi), panax japonicas (Zhujieshen), atractylodes macrocephala koidz (Baizhu), radix paeoniae alba (Baishao), bupleurum (Chaihu), chrysanthemum (Juhua), rhizoma cyperi (Xiangfu) and gastrodin (Tianma), whose aqueous extract was fermented with lactobacillus, bacillus aceticus and saccharomycetes. Shuan-Tong-Ling is a formula used to treat brain diseases including ischemic stroke, migraine, and vascular dementia. Shuan-Tong-Ling attenuated H2O2-induced oxidative stress in rat microvascular endothelial cells. However, the potential mechanism involved in these effects is poorly understood. Rats were intragastrically treated with 5.7 or 17.2 mL/kg Shuan-Tong-Ling for 7 days before middle cerebral artery occlusion was induced. The results indicated Shuan-Tong-Ling had a cerebral protective effect by reducing infarct volume and increasing neurological scores. Shuan-Tong-Ling also decreased tumor necrosis factor-α and interleukin-1β levels in the hippocampus on the ischemic side. In addition, Shuan-Tong-Ling upregulated the expression of SIRT1 and Bcl-2 and downregulated the expression of acetylated-protein 53 and Bax. Injection of 5 mg/kg silent information regulator 1 (SIRT1) inhibitor EX527 into the subarachnoid space once every 2 days, four times, reversed the above changes. These results demonstrate that Shuan-Tong-Ling might benefit cerebral ischemia/reperfusion injury by reducing inflammation and apoptosis through activation of the SIRT1 signaling pathway.

Key words: nerve regeneration, traditional Chinese medicine, ferment, Shuan-Tong-Ling, middle cerebral artery occlusion, cerebral ischemia/reperfusion, silent information regulator 1, inflammation, apoptosis, tumor necrosis factor-α, interleukin-1β, Bcl-2, Bax, acetylated-protein 53, neural regeneration