Caveolae在剪切力诱导过氧化氢引起小鼠肠系膜动脉舒张中的作用  

Role of Caveolae in shear stress-induced hydrogen peroxide release for mesenteric artery relaxation in mice

作　　者：孙玮 邢守欣 贾青 刘振东 张华 赵颖馨 柴强 Sun Wei;Xing Shouxin;Jia Qing;Liu Zhendong;Zhang Hua;Zhao Yingxin;Chai Qiang(School of Clinical and Basic Medical Sciences,Shandong First Medical University&Shandong Academy of Medical Sciences,Jinan 250000,Shandong Province,China)

机构地区：[1]山东第一医科大学(山东省医学科学院)临床与基础医学院(基础医学研究所),济南250000

出　　处：《中华老年心脑血管病杂志》2023年第7期746-750,共5页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

基　　金：国家自然科学基金(81470489,81973139,81670432)。

摘　　要：目的探讨Caveolae在剪切力诱导的过氧化氢引起小鼠肠系膜动脉舒张中的作用。方法随机选取野生型或Cav-1基因敲除(Cav-1^(-/-))小鼠分离肠系膜动脉进行血管实验分组:野生型组,野生型+Catalase组,野生型去内皮(WT-endo)组,WT-endo+Catalase组,Cav-1^(-/-)组,Cav-1^(-/-)去内皮(Cav-1^(-/-)-endo)组,Cav-1^(-/-)+Catalase组和Cav-1^(-/-)-endo+Catalase组(n=5),进行剪切力诱导的血管舒张(SSD)实验。细胞实验:(1)分别给予小鼠主动脉内皮细胞0、0.5、1h剪切力[15dyn/cm^(2)(1dyn=10-5N)],处理;(2)选取小鼠主动脉内皮细胞分为对照组,阴性对照组和Cav-1敲减组(n=11),在剪切力下,采用Westernbolt检测Cav-1和超氧化物歧化酶(SOD1)及Catalase蛋白表达。结果与野生型组比较,Cav-1^(-/-)组25dyn/cm^(2)剪切力的SSD百分比明显下降[(20.4±1.9)%vs(58.4±1.1)%,P=0.000],WT-endo组25dyn/cm^(2)剪切力的SSD百分比明显下降[(23.9±1.3)%vs(58.4±1.1)%,P=0.000]。Cav-1^(-/-)组与Cav-1^(-/-)-endo血管组中SSD百分比比较,差异无统计学意义(P>0.05)。与野生型组比较,野生型+Catalase组剪切力25dyn/cm^(2)时SSD百分比明显降低,差异有统计学意义(P=0.000)。WT-endo组与WT-endo+Catalase组SSD百分比比较,差异无统计学意义(P>0.05)。与细胞施剪切力0h比较,当小鼠主动脉内皮细胞施加剪切力1h后,细胞中SOD1和Catalase表达明显增加(P<0.05,P<0.01)。Cav-1^(-/-)组与Cav-1^(-/-)+Catalase组血管SSD百分比比较,差异无统计学意义(P>0.05)。Cav-1^(-/-)-endo组与Cav-1^(-/-)-endo+Catalase组SSD百分比比较,差异无统计学意义(P>0.05)。结论Caveolae促进剪切力诱导内皮细胞释放H2O2引起SSD。Objective To investigate the role of Caveolae in shear stress-induced relaxation of mesenteric artery in mice induced by hydrogen peroxide(H_(2)O_(2)).Methods Mouse mesenteric arteries were isolated from wild-type(WT)and Cav-1^(-/-)mice,respectively,and the obtained vessel samples were divided into WT,WT+Catalase,WT-endo(removing endothelial cells),WT-endo+Catalase,Cav-1^(-/-),Cav-1^(-/-)+Catalase,Cav-1^(-/-)-endo,and Cav-1^(-/-)-endo+Catalase groups,with 5 samples in each group.Then shear stress-induced diastole(SSD)was carried out.Shear stress[15 dyn/cm^(2)(1 dyn=10^(-5)N)]was applied for a time gradient of 0,0.5,and 1 h to mouse aortic endothelial cells.Then the cells were divided into control,negative control and Cav-1 knockdown groups(n=11).Under shear stress,the expression levels of Cav-1,SOD1 and Catalase were de-tected by Western blotting.Results Under a shear stress of 25 dyn/cm^(2),when compared with the SSD in the WT group[(58.4±1.1)%],SSD was obviously lower in the Cav-1^(-/-)group[(20.4±1.9)%,P=0.000]and the WT-endo group[(23.9±1.3)%,P=0.000].There was no difference in the percentage between the Cav-1^(-/-)group and Cav-1^(-/-)-endo group(P>0.05).The percentage was reduced in the WT+Catalase group than the WT group(P=0.000).No statistical difference was seen in the percentage between the WT-endo and WT-endo+Catalase groups(P>0.05).Shear stress for 1 h significantly increased the expression of SOD1 and Catalase when compared no stress(P<0.05,P<0.01).There were no obvious differences in the SSD percentage between Cav-1^(-/-)group and Cav-1^(-/-)-Catalase group,or between Cav-1^(-/-)-endo group and Cav-1^(-/-)-endo+Catalase group(P>0.05).Conclusion Caveolae promotes shear stress-induced release of H_(2)O_(2) from endothelial cells and thus causes SSD.

关 键 词：细胞质膜微囊 过氧化氢 肠系膜动脉 血管舒张 内皮细胞 剪切力 Cav-1基因敲除小鼠 

分 类 号：R572.3[医药卫生—消化系统]