大黄酚抑制自噬改善HIBI新生大鼠脑组织病理损伤和炎症反应  

Chrysophanol inhibits autophagy to improve brain histopathological damage and inflammatory response in neonatal rats with hypoxic-ischemic brain injury

作　　者：邴小三 望燕妮 赵申[1] 肖惠玲 黄亚萍 BING Xiao-San;WANG Yan-Ni;ZHAO Shen;XIAO Hui-Ling;HUANG Ya-Ping(Department of Pediatrics,Xiangyang Central Hospital Affiliated to Hubei University of Arts and Science,Xiangyang 441000,China)

机构地区：[1]湖北文理学院附属襄阳市中心医院儿科,襄阳441000 [2]三峡大学第一临床医学院附属宜昌市中心人民医院儿科,宜昌441000

出　　处：《中国免疫学杂志》2019年第24期3015-3020,共6页Chinese Journal of Immunology

基　　金：湖北省自然科学基金(2017CFB136)资助

摘　　要：目的:探讨大黄酚(CP)对缺氧缺血性脑损伤(HIBI)模型新生大鼠脑组织病理损伤和炎症反应的作用及其可能机制。方法:大鼠随机分假手术组(Sham)、模型组(HIBI)、尼莫地平(NIM)模型组(HIBI+NIM)、模型给药组(HIBI+CP 2.5、5、10),采用结扎颈总动脉结合低氧环境法建立HIBI新生大鼠模型。造模24 h后检测大鼠脑组织含水量,HE染色观察大鼠脑组织病理学改变,ELISA检测大鼠脑组织炎症因子水平,Western blot检测大鼠自噬相关蛋白表达水平。另取大鼠随机分假手术组(Sham)、模型组(HIBI)、雷帕霉素(RAP)模型组(HIBI+RAP)、模型给药组(HIBI+CP),于造模后第28天采用Morris水迷宫测试大鼠学习和记忆能力。结果:与模型组相比,大黄酚能降低大鼠脑组织含水量(P<0.05或P<0.01),改善脑组织病理损伤;降低肿瘤坏死因子(TNF-α)、诱导性一氧化氮合酶(iNOS)和IL-6含量(P<0.01),而增加抗炎因子IL-10的脑组织含量(P<0.01);下调自噬微管相关蛋白1轻链3(LC3)Ⅱ/LC3Ⅰ、Beclin1和Bax表达水平(P<0.05或P<0.01),而上调p62/Sequestosome1 (SQSTM1)和Bcl-2表达水平(P<0.05或P<0.01);同时,抑制mTOR/p70S6K自噬信号通路磷酸化激活(P<0.05或P<0.01);最后,改善模型大鼠的学习和记忆能力(P<0.01)。结论:大黄酚能改善HIBI大鼠脑组织病理损伤及炎症反应,其机制可能与抑制脑组织异常自噬有关。Objective:To investigate the effect and possible mechanism of chrysophanol on histopathological injury and inflammatory response in neonatal rats with hypoxic-ischemic brain injury.Methods:Rats were randomly divided into sham group(Sham),model group(HIBI),nimodipine(NIM) model group(HIBI+NIM) and model administration group(HIBI+CP 2.5,5,10).The neonatal HIBI rat model was established by ligating common carotid artery and hypoxic environment.After 24 hours,the water content of rat brain tissue was measured,the pathological changes of rat brain tissue were observed by HE staining,the levels of inflammatory factors in rat brain tissue were detected by ELISA,and the expression of autophagy-related protein was detected by Western blot.In addition,rats were randomly divided into sham group(Sham),HIBI group(HIBI),rapamycin(RAP) model group(HIBI+RAP) and HIBI+CP group(HIBI+CP).The learning and memory abilities of rats were tested by Morris water maze on the 28 th day after operation.Results:Compared with the model group,chrysophanol could decrease the water content of brain tissue(P<0.05 or P<0.01),improve the pathological damage of brain tissue,reduce the contents of tumor necrosis factor(TNF-α),inducible nitric oxide synthase(iNOS) and interleukin-6(IL-6) and increase the content of anti-inflammatory factor IL-10 in brain tissue(P<0.01).The expression levels of light chain 3(LC3)Ⅱ/LC3Ⅰ,Beclin1 and Bax were down-regulated(P<0.05 or P<0.01),while the expression levels of p62/Sequestosome1(SQSTM1) and Bcl-2 were up-regulated(P<0.05 or P<0.01);meanwhile,the phosphorylation activation of mTOR/p70 S6 K autophagy signaling pathway was inhibited(P<0.05 or P<0.01);finally,the learning and memory abilities of model rats were improved(P<0.01).Conclusion:CP can improve the pathological damage and inflammation of brain tissue in HIBI rats,and its mechanism may be related to the inhibition of abnormal autophagy of brain tissue.

关 键 词：大黄酚 缺氧缺血性脑损伤 炎症反应 自噬 

分 类 号：R285.5[医药卫生—中药学]