摘要
目的:从P62/Keap1信号通路探讨清热化瘀方对脑缺血再灌注损伤大鼠神经保护的作用机制。方法:线栓法制备局灶性脑缺血大鼠模型,将160只大鼠随机分为4组:假手术组(SO组)、模型组(MCAO组)、清开灵组(QKL组)、清热化瘀方组(QRHY组),每组按再灌注时间点分为4个亚组。采用TTC法测量脑梗死体积,qRTPCR和免疫组化检测P62、Keap1 mRNA及蛋白表达变化。结果:QKL组较MCAO组梗死体积明显减小(P<0.05),QRHY组脑梗死体积较QKL组进一步缩小(P<0.05)。MCAO组Keap1 mRNA及蛋白表达均于再灌注后12h开始明显上升(P<0.01),24h达高峰(P<0.01),随再灌注时间延长其表达逐渐下降;而P62 mRNA及蛋白表达时相变化则与之相反(P<0.05,P<0.01);与MCAO组比较,两用药组均升高P62、降低Keap1表达(P<0.05,P<0.01),而QRHY组较QKL组进一步升高P62表达,降低Keap1的表达(P<0.05,P<0.01)。结论:清热化瘀方可能通过调节P62/Keap1信号通路达到减轻脑缺血再灌注损伤,保护神经元。
Objective:To investigate the effects of Qingre Huayu Prescription on rats with cerebral ischemia-reperfusion injury(I/R)through P62/Keap1 signaling pathway.Methods:The focal cerebral ischemia rats model was prepared by suture method,and 160 SD rats were randomly divided into 4 groups:sham operation group(SO),model group(MCAO),Qingkailing group(QKL)and Qingre Huayu Prescription group(QRHY).Each group was further divided into 4 subgroups after I/R.Cerebral infarction volume were tested by TTC staining method,and the expression changes of P62 and Keap1 mRNA and its protein were observed by qRT-PCR and immunohistochemistry,separately.Results:Compared with MCAO group,the brain infarct volume was decreased(P<0.05).QRHY could further decrease brain infarct volume than that of QKL(P<0.05).The expression of Keap1 mRNA and its protein in MCAO group increased significantly after I/R(P<0.01),and 24h reached the peak(P<0.01),then decreased continuously.But the expression changes of P62 mRNA and its protein were just the opposite at each point(P<0.05,P<0.01).Compared with MCAO group,the exprossion of P62 was increased and Keap1 was decreased in QKL group and QRHY group,QRHY could further induce the expression of P62 and decrease the expression of Keap1 than that of QKL group(P<0.05,P<0.01).Conclusion:Qingre Huayu Prescription could protect neurons and decrease I/R injury through regulating the P62/keap1 signaling pathway after I/R in rats.
作者
胡跃强
廖泰荣
唐农
秦红玲
李媛媛
王启芝
HU Yue-qiang;LIAO Tai-rong;TANG Nong;QIN Hong-ling;LI Yuan-yuan;WANG Qi-zhi(The First Affiliated Hospital of Guangxi University of Chinese Medicine,Nanning 530023,China;Guangxi University of Chinese Medicine,Nanning 530001,China)
出处
《中华中医药杂志》
CAS
CSCD
北大核心
2019年第8期3409-3412,共4页
China Journal of Traditional Chinese Medicine and Pharmacy
基金
国家自然科学基金项目(No.81560759)~~
