白藜芦醇对抗线粒体电压依赖性阴离子通道介导心肌损伤作用的研究  

Resveratrol protects against anoxia/reoxygenation injury mediated by mitochondrial VDAC in cardiomyocytes

作　　者：廖章萍[1,2] 章志玲[3] 邹逢琳[2] 尹淑华[2] 刘丹[2] 汤蕾[2] 何明[1,2] 

机构地区：[1]南昌大学第一附属医院江西省高血压病研究所,江西南昌330006 [2]南昌大学药学院药理学与分子治疗学教研室 [3]江西省人民医院心内科,江西南昌330006

出　　处：《中国药理学通报》2011年第4期477-481,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No30760075,30960449)

摘　　要：目的从细胞水平探讨白藜芦醇抗心肌损伤保护作用机制,明确其与线粒体电压依赖性阴离子通道(VDAC)的关系。方法以pFLAG质粒为载体,构建VDAC1真核表达载体pFLAG-VDAC1。H9c2心肌细胞随机分为5组,Control组、缺氧/复氧(A/R)组、白藜芦醇组、pFLAG-VDAC1-白藜芦醇组和pFLAG-白藜芦醇组。Western blot法测定VDAC1的蛋白表达,MTT法检测细胞存活率,生化自动分析仪测定LDH、CPK活性,线粒体肿胀实验检测线粒体通透性转换孔道(mPTP)的开放。结果 A/R处理后,VDAC1表达上调,细胞存活率下降,LDH和CPK活性增高,mPTP开放;而白藜芦醇则能抑制VDAC1的上调,并降低mPTP开放程度,对抗A/R损伤;但VDAC1高表达的pFLAG-VDAC1-白藜芦醇组则可取消白藜芦醇的心肌保护作用。结论白藜芦醇抗A/R损伤作用与VDAC1密切相关,其可通过下调VDAC1从而防止mPTP的开放,保护心肌细胞。Aim To investigate the protective effects of Resveratrol in H9c2 cardiomyocytes subjected to anoxia/reoxygenation（A/R） injury and the underlying mechanism related to voltage-dependent anion channel（VDAC1）.Methods H9c2 cells were randomly divided into five groups as follows： control,A/R,Resveratrol,pFLAG-VDAC1-Resveratrol and pFLAG-Resveratrol groups.The expression of VDAC1 was determined by Western blot.Cellular injury was evaluated by measuring cell viability,LDH and CPK release.Opening of mitochondrial permeability transition pore（mPTP） was determined by Ca2＋-induced swelling of isolated cardiac mitochondria.Results VDAC1 expression was up-regulated in A/R group,which was inhibited in Resveratrol group.Resveratrol protected H9c2 cells against A/R injury and inhibited opening of mPTP.However,the protective effects of Resveratrol were abandoned in pFLAG-VDAC1-Resveratrol with up-regulation of VDAC1.Conclusion Resveratrol protects cardiomyocyte against A/R injury via down-regulation of VDAC1.

关 键 词：白藜芦醇 线粒体 线粒体通透性转换孔道 电压依赖性阴离子通道 缺氧复氧 心肌细胞 

分 类 号：R322.11[医药卫生—人体解剖和组织胚胎学] R284.1[医药卫生—基础医学]