线粒体乙醛脱氢酶在大鼠糖尿病心肌病中的表达及意义  

Expression of mitochondrial aldehyde dehydrogenase in rat diabetic cardiomyopathy

作　　者：王晓梅[1] 叶红伟[1] 康品方[2] 王洪巨[2] 高琴[1] 李正红[1] 

机构地区：[1]蚌埠医学院生理学教研室,安徽蚌埠233030 [2]蚌埠医学院第一附属医院心血管内科,安徽蚌埠233004

出　　处：《中国药理学通报》2012年第3期379-383,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81000074);安徽省自然科学基金资助项目(No 090413097)

摘　　要：目的观察线粒体乙醛脱氢酶2(aldehyde dehydrogen-ase 2,ALDH2)在糖尿病大鼠不同病程阶段心肌损伤中表达,并分析其作用。方法采用STZ腹腔注射诱导糖尿病大鼠模型,造模成功后分别于4周、8周、12周行离体心脏灌流,测定心室动力学指标和心肌组织SOD活性、MDA和羟脯氨酸含量变化。Real-Time qPCR测定左心室前壁心尖组织线粒体ALDH2 mRNA的表达。结果与正常对照组相比,糖尿病4周组左室发展压和左心室内压最大上升和下降速率无明显变化,但心肌SOD活性降低,MDA和羟脯氨酸含量明显增高,ALDH2 mRNA表达降低;糖尿病8周、12周组左室发展压,左心室内压最大上升和下降速率均降低,心肌SOD活性明显降低,MDA和羟脯氨酸含量明显增高,ALDH2mRNA表达降低;且随着病程的延长,糖尿病大鼠不同时间段相比,动力学、心肌SOD活性、ALDH2 mRNA表达进一步降低,MDA和羟脯氨酸含量明显增高。结论随糖尿病病程的延长,心肌ALDH2表达逐渐降低,可能与其抗氧化能力逐渐下降,心肌纤维化程度不断加重密切相关。Aim To investigate the role of mitochondrial aldehyde dehydrogenase 2（ALDH2） in different stages of rat diabetic cardiomyopathy（DM） and analyze the related mechanism.Methods Diabetic model in SD rat was induced by a single intraperitoneal injection of streptozoticin（STZ）.Hearts isolated from DM 4 wk,8 wk,12 wk rats were perfused on a langendorff apparatus.The ventricular hemodynamic parameters,SOD activity,MDA and hydroxyproline（Hp） contents were measured.The expression of ALDH2 at mRNA level of left anterior myocardium was detected by Real-Time qPCR analysis.Results In contrast to normal group,there were no particular changes of left ventricular developed pressure and maximal rise/fall rate of left ventricular pressure in DM 4 wk group,but MDA and Hp contents were increased,SOD activity and the expression of ALDH2 mRNA level were reduced.In DM 8 wk and DM 12 wk group,there were significant decreases of left ventricular developed pressure,maximal rise/fall rate of left ventricular pressure and SOD activity,MDA and Hp contents were increased.The expression of ALDH2 mRNA level was reduced.With the diabetic cardiomyopathy development,the ventricular hemodynamic parameters,SOD activity and ALDH2 mRNA level were further reduced,and MDA,Hp contents were increased.Conclusion With the development of diabetes,the expression of heart mitochondrial ALDH2 is further decreased,which may be related to the decrease of antioxidant ability,and the aggravation of cardiac fibrosis.

关 键 词：糖尿病心肌 线粒体乙醛脱氢酶2 荧光定量PCR 超氧化物歧化酶 丙二醛 羟脯氨酸 

分 类 号：R-332[医药卫生] R322.11