摘要
目的:探讨星蒌承气汤(Xinglou Chengqi decoction,XCD)对急性缺血性卒中小鼠脑–肠轴的影响。方法:根据中医辨证分型标准,采用改良Longa法建立痰热腑实证脑缺血再灌注模型。60只无特定病原体的雄性C57BL/6小鼠随机分为5组,36只经抗生素处理的(ABX)小鼠随机分为三组。采用酶联免疫吸附试验检测盲肠去甲肾上腺素(NE)和胃动素(MTL),免疫组织化学方法检测盲肠酪氨酸羟化酶(TH)蛋白表达水平,免疫荧光法检测Iba-1和胶质纤维酸性蛋白(GFAP)表达水平,流式多因子技术检测血清炎症因子含量。结果:与假手术组相比,大脑中动脉闭塞(MCAO)组盲肠组织中TH的表达水平显著升高(P=0.015)。与假手术组相比,MCAO组大鼠MTL水平显著升高(P<0.001),与MCAO组相比XCD组和尼莫地平(Nim)组大鼠血清MTL水平明显降低(P=0.003和P=0.007)。MCAO组星形胶质细胞和小胶质细胞明显激活,而XCD组激活程度低于MCAO组。ABX小鼠中星形胶质细胞和小胶质细胞在ABX–MCAO组明显激活,而ABX–XCD组激活程度较低。ABX–XCD组白细胞介素22水平较ABX–MCAO组显著升高(P=0.021)。结论:星蒌承气汤对急性缺血性卒中小鼠脑–肠轴的免疫通路有明显的调节作用,去除肠道菌群使该作用明显减弱。
Objective:To explore the effect of Xinglou Chengqi decoction(XCD)on the brain-gut axis in mice with acute ischemic stroke.Methods:A cerebral ischemia-reperfusion model identified as phlegm-heat and fu-organ excess pattern was established by reforming the Longa method and based on the diagnostic criteria of traditional Chinese medicine.Sixty specific-pathogen free male C57BL/6 mice were randomly divided into five groups,and 36 antibiotic-treated(ABX)mice were randomly divided into three groups.Cecum norepinephrine(NE)and motilin(MTL)were detected by enzyme-linked immunosorbent assay,cecum tyrosine hydroxylase(TH)protein expression level was detected by immunohistochemistry,Iba-1 and glial fibrillary acidic protein(GFAP)expression levels were detected by immunofluorescence,and serum inflammatory factor contents were detected using the flow multifactor technique.Results:Compared to the sham group,a significant increase in TH expression level was observed in the cecum in the middle cerebral artery occlusion(MCAO)group(P=.015).MTL levels were significantly increased in the MCAO group compared with the sham group(P<.001)and significantly decreased in the XCD and nimodipine(Nim)groups compared with the MCAO group(P=.003 and P=.007,respectively).Astrocytes and microglia were markedly activated in the MCAO group,whereas activationwas decreased in the XCD group compared to the MCAO group.Antibiotic-treated(ABX)mice astrocytes and microglia were obviously activated in the ABX-MCAO group,and activation tended to be lower in the ABX-XCD group.Interleukin-22 level significantly increased in the ABX-XCD group compared with the ABX-MCAO(P=.021).Conclusion:XCD has a significant regulatory effect on the immune pathway of the brain-gut axis in mice with acute ischemic stroke,while the removal of the gut microbiota attenuates the effect considerably.
作者
于瑞芸
高强
张超
杨海欢
姚兴伟
孙逸坤
马洪明
胡汉华
马大勇
Ruiyun Yu;Qiang Gao;Chao Zhang;Haihuan Yang;Xingwei Yao;Yikun Sun;Hongming Ma;Han-Hwa Hu;Dayong Ma(Dongzhimen Hospital,Beijing University of Chinese Medicine,Beijing,100700,China;School of Traditional Chinese Medicine,Beijing University of Chinese Medicine,Beijing,102488,China;Clinical Laboratory,Dongzhimen Hospital,Beijing University of Chinese Medicine,Beijing,100700,China;Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing,Dongzhimen Hospital,Beijing University of Chinese Medicine,Beijing,100700,China;Department of Neurology,Dongzhimen Hospital,Beijing University of Chinese Medicine,Beijing,100700,China;Graduate Institute of Clinical Medicine,College of Medicine,Taipei Medical University,10031,Taipei,China;Cerebrovascular Treatment and Research Center,College of Medicine,Taipei Medical University,10031,Taipei,China;Department of Neurology,Taipei Medical University-Shaung Ho Hospital,23561,New Taipei,China)
基金
supported by the National Natural Science Foundation of China(81704049).
关键词
星蒌承气汤
急性缺血性中风
痰热腑实证
脑–肠轴
免疫炎症
Xinglou Chengqi decoction
Acute ischemic stroke
Phlegm-heat and fu-organ excess pattern
Brain-gut axis
Immune inflammation
作者简介
通信作者:马大勇,E-mail address:a3153@bucm.edu.cn
