补阳还五汤对Cav-1敲除小鼠脑缺血后mTOR通路的影响 |
| |
作者姓名: | 陈博威 周胜强 易健 罗琳 刘柏炎 谢勇 |
| |
作者单位: | 湖南中医药大学,湖南长沙410208;湖南省中医药研究院附属医院,湖南长沙410006;湖南中医药大学第一附属医院,湖南长沙410007;湖南中医药大学,湖南长沙410208;益阳医学高等专科学校,湖南益阳413000;湖南中医药大学第二附属医院,湖南长沙410005 |
| |
基金项目: | 湖南省中医药局项目;国家自然科学基金;湖南省自然科学基金 |
| |
摘 要: | 目的探讨小窝蛋白(caveolin-1,Cav-1)对脑缺血后哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)信号通路的影响及补阳还五汤抗脑缺血的可能作用机制。方法将Cav-1基因敲除(knock out,KO)与野生型(wild type,WT)小鼠随机分为KO假手术组、KO模型组、KO补阳还五汤组(补阳组)、WT假手术组、WT模型组及WT补阳组。采用大脑中动脉栓塞法建立脑缺血模型,干预14 d后观察小鼠神经功能评分;免疫组化检测大脑mTOR、磷酸化核糖体S6蛋白激酶(phospho-ribosomal S6 kinase,p-S6K1)、磷酸化真核细胞翻译起始因子4E结合蛋白-1(phospho-eukaryotic initiation factor 4E-binding protein 1,p-4EBP1)的蛋白表达;qRT-PCR检测大脑mTOR的mRNA水平。结果与同类假手术组比较,其他4组神经功能评分、mTOR、p-S6K1、p-4E-BP1蛋白表达及mTOR mRNA表达明显上升(P<0.01);与同类模型组比较,KO补阳组、WT补阳组神经功能评分明显下降(P<0.01),各蛋白表达与mRNA表达明显上升(P<0.01);与WT模型组比较,KO模型组神经功能评分上升(P<0.05),各蛋白与m RNA表达明显下降(P<0.01);与WT补阳组比较,KO补阳组神经功能评分明显上升(P<0.01),各蛋白及m RNA明显下降(P<0.01)。结论Cav-1基因的缺失会导致mTOR通路活性降低并加重脑缺血后神经功能损伤;补阳还五汤可能通过Cav-1调控mTOR信号通路的活性,发挥抗脑缺血损伤的作用。
|
关 键 词: | 脑缺血 MTOR信号通路 补阳还五汤 Cav-1基因敲除 |
Effects of Buyang Huanwu Decoction on mTOR Pathway in Cav-1 Knock Out Mice after Cerebral Ischemia |
| |
Authors: | CHEN Bowei ZHOU Shengqiang YI Jian LUO Lin LIU Baiyan XIE Yong |
| |
Institution: | (Hunan University of Chinese Medicine,Changsha,Hunan 410208,China;The Affiliated Hospital of Hunan Provincial Academy of Traditional Chinese Medicine,Changsha,Hunan 410006,China;The First Affiliated Hospital of Hunan University of Chinese Medicine,Changsha,Hunan 410007,China;Yiyang Medical College,Yiyang,Hunan 413000,China;The Second Affiliated Hospital of Hunan University of Chinese Medicine,Changsha,Hunan 410005,China) |
| |
Abstract: | Objective To investigate the effects of caveolin-1(Cav-1)on mammalian target of rapamycin(mTOR)signaling pathway after cerebral ischemia and the possible mechanism of Buyang Huanwu Decoction(BHD)in anti-cerebral ischemia.Methods Cav-1 knock out mice(KO)and wild type mice(WT)were randomly divided into a KO sham operation group,a KO model group and a KO BHD group,a WT sham operation group,a WT model group,and a WT BHD group.Cerebral ischemia model was established by middle cerebral artery occlusion(MCAO).After 14 days of intervention,the neurological function scores of each group were observed.The protein expression of mTOR,phospho-Ribosomal protein S6 kinase beta-1(p-S6 K1),phospho-eukaryotic initiation factor 4 E-binding protein 1(p-4 E-BP1)were detected by immunohistochemical method,and m TOR mRNA was detected by qRT-PCR.Results Compared with the sham group,the neurological function scores,the expression of mTOR,pS6 K1,p-4 E-BP1 protein and mTOR mRNA of the other 4 groups were significantly increased(P<0.01).Compared with the similar model group,the neurological function scores of the KO BHD group and the WT BHD group decreased significantly(P<0.01).The expression of each protein and mRNA increased significantly(P<0.01).Compared with the WT model group,the neurological function scores of the KO model group increased(P<0.05),and the expression of each protein and mRNA decreased significantly(P<0.01).Compared with the WT BHD group,the neurological function scores of the KO BHD group increased significantly(P<0.01),and each protein and mRNA decreased significantly(P<0.01).Conclusion The deletion of Cav-1 gene can reduce the activity of mTOR pathway and aggravate the neurological damage after cerebral ischemia;BHD may regulate the activity of mTOR signaling pathway through Cav-1 and play a role in resisting cerebral ischemic injury. |
| |
Keywords: | cerebral ischemia mTOR signaling pathway Buyang Huanwu Decoction Cav-1 gene knock out |
本文献已被 CNKI 维普 万方数据 等数据库收录! |
|