PPARγ激动剂罗格列酮对缺氧／复氧大鼠心肌细胞氧化应激和凋亡的影响  

PPARγ agonist rosiglitazone alleviates hypoxia/reoxygenation-induced oxidative stress and apoptosis in rat cardiac myocytes

作　　者：姚友杰[1] 耿登峰[1] 王景峰[1] 杨敏华[2] 张玉玲[1] 聂如琼[1] 周淑娴[1] 

机构地区：[1]中山大学附属第二医院心内科,广东广州510120 [2]河南省中医院急诊科,河南郑州450002

出　　处：《南方医科大学学报》2009年第4期689-693,696,共6页Journal of Southern Medical University

基　　金：教育部博士点基金(20060558029);广东省博士启动基金(5300704)

摘　　要：目的观察不同浓度PPARγ激动剂罗格列酮对缺氧/复氧大鼠心肌细胞氧化应激影响及细胞活力和凋亡情况。方法建立大鼠心肌细胞缺氧/复氧模型。培养大鼠心肌细胞分为5组:Ⅰ组(正常组)、Ⅱ组(20μmo/LROS组)、Ⅲ组(I/R组)、Ⅳ组(I/R+20μmol/LROS组)、Ⅴ组(I/R+80μmol/LROS组),Ⅳ组和Ⅴ组在缺氧/复氧前12h经ROS处理。分别在光镜和透射电镜下观察缺氧/复氧后各组心肌细胞形态改变,采用硫代巴比妥酸法测定丙二醛(MDA)含量,采用黄嘌呤氧化酶法测定超氧化物岐化酶(SOD)活力,采用2,4-二硝基苯肼法测定乳酸脱氢酶(LDH)含量,采用MTT法比较各组心肌细胞活力和采用流式细胞术测定各组心肌细胞凋亡率。结果与Ⅰ组相比,Ⅲ组的MDA和LDH含量及细胞凋亡率明显升高(P<0.05),SOD含量和细胞活力降低(P<0.05);Ⅳ组和Ⅴ组MDA和LDH含量及细胞凋亡率较Ⅲ组降低(P<0.05)而SOD含量和细胞活力增加(P<0.05)。Ⅴ组MDA和LDH含量及细胞凋亡率较Ⅳ组降低(P<0.05)而SOD含量和细胞活力增加(P<0.05)。电镜下观察到Ⅲ组(I/R组)心肌细胞形态出现明显凋亡损伤改变,凋亡小体形成,而Ⅴ组改变轻微。结论罗格列酮可以显著减轻心肌细胞缺氧/复氧导致的氧化应激损伤,改善细胞活力和减轻心肌细胞凋亡率,并存在量效关系。Objective To observe the effects of different concentrations of PPAR 3＇ agonist rosiglitazone on hypoxia/reoxygenation-induced oxidative stress, cell viability and apoptosis in rat cardiac myocytes. Methods Cultured rat cardiac myocytes were divided into 5 groups, namely group I （normal group）, group Ⅱ （20 μmo/L ROS group）, group Ⅲ （FR group）, group Ⅳ （I/R＋20 μmo/L ROS group）, and group V （I/R＋80 μmo/L ROS group）. Group IV and group V were treated with rosiglitazone 12 h before hypoxia/reoxygenation. The changes in cell morphology were observed under optical and transmission electron microscopy, and levels of malondialdehyde （MDA）, superoxide dismutase （SOD） activity, and lactate dehydrogenase （LDH） content were determined after the treatment. MTT assay was performed to assess the cell viability and flow cytometry was used to analyze the cell apoptosis. Results Hypoxia/reoxygenation resulted in significantly increased MDA and LDH contents and apoptosis of the cardiac myocytes （P〈0.05）, but lowered SOD activity and the cell viability （P〈0.05）. The MDA and LDH contents and apoptotic rate were significantly lower but SOD content and cell vitality significantly higher in groups IV and V than in group m （P〈0.05）. Group V showed significantly lower MDA and LDH contents and apoptotic rate but higher but SOD content and cell vitality than group IV （P〈0.05）. Electron microscopy revealed obvious apoptotic changes in group Ⅲ, and only mild changes were found in group V. Conclusion Rosiglitazone can significantly reduce hypoxia/reoxygenation-induced oxidative stress in cardiac myocytes, improve the cell viability and dose-dependently reduce the apototic rate of the cardiac myocytes.

关 键 词：心肌细胞 缺氧/复氧损伤 细胞凋亡 罗格列酮 

分 类 号：R96[医药卫生—药理学]