罗格列酮对高糖高胰岛素诱导心肌细胞肥大的抵抗作用及其机制  

Resistance of rosiglitazone to cardiomyocyte hypertrophy induced by high glucose and insulin and relevant mechanism

作　　者：彭晓凤[1] 吴芹[2] 蒋青松[1] 

机构地区：[1]重庆医科大学药理学教研室,重庆400016 [2]遵义医学院药理教研室,贵州遵义563003

出　　处：《中国生物制品学杂志》2012年第11期1503-1507,共5页Chinese Journal of Biologicals

基　　金：重庆市自然科学基金计划项目(CSTC;2010BB5108);高等学校博士学科点专项科研基金资助课题(20105503120005)

摘　　要：目的研究罗格列酮(Rosiglitazone,RSG)对高糖高胰岛素(High glucose and insulin,HGI)诱导心肌肥大中的抵抗作用及其机制。方法用HGI培养SD大鼠乳鼠心肌细胞,建立心肌细胞肥大模型,并给予不同浓度的RSG处理;以细胞表面积、蛋白含量和心钠肽(Atrial natriuretic peptide,ANP)基因mRNA的水平为心肌肥大指标,观察RSG对HGI诱导心肌肥大的作用;Real-time PCR和Western blot分别检测过氧化物酶体增殖物激活受体-γ(Peroxisome proliferator-activated receptor-γ,PPAR-γ)和内皮型一氧化氮合酶(Endothelial nitric oxide synthase,eNOS)基因mRNA水平和蛋白的表达水平;双抗体夹心ABC-ELISA法和硝酸还原法分别检测eNOS和NO的含量。结果 HGI成功诱导大鼠心肌细胞肥大;RSG呈浓度依赖性地抑制HGI诱导的心肌细胞肥大,并明显上调HGI所致的PPAR-γ和eNOS基因mRNA水平的降低,同时增加PPAR-γ蛋白的表达水平、eNOS和NO的含量(P均<0.05)。PPAR-γ抑制剂GW9662及NOS抑制剂L-硝基-精氨酸甲酯(L-NAME)均可阻断RSG的上述作用。结论 RSG通过激活PPAR-γ受体、增加eNOS的含量、促进NO释放,从而产生抗HGI诱导的心肌细胞肥大作用。Objective To investigate the resistance of rosiglitazone（RSG） to cardiomyocyte hypertrophy induced by high glucose and insulin（HGI） as well as the relevant mechanism.Methods The cardiomyocytes of suckling SD rats were cultured under HGI condition to establish cardiomyocyte hypertrophy model.The model rats were treated with RSG at various concentrations.The effect of RSG on HGI-induced cardiomyocyte hypertrophy was observed using the cell surface area,total protein content and atrial natriuretic peptide（ANP） mRNA level as indicators.The expression of peroxisome proliferator-activated receptor-γ（PPAR-γ） and endothelial nitric oxide synthase（eNOS） at mRNA level were determined by real-time PCR,while those at protein level by Western blot.The eNOS and nitric oxide（NO） contents were determined by double antibody sandwich ABC-ELISA and nitrate reduction method respectively.Results HGI induced cardiomyocyte hypertrophy in rats successfully.RSG showed dose-dependent inhibitory effect on HGI-induced cardiomyocyte hypertrophy,up-regulated HGI-induced decrease of PPAR-γ and eNOS mRNA levels,and increased the expression level of PPAR-γ protein as well as eNOS and NO contents（each P 0.05）.However,both the PPAR-γ inhibitor GW9662 and NOS inhibitor L-NAME blocked the above-mentioned effects of RSG.Conclusion RSG resisted HGI-induced cardiomyocyte hypertrophy by activating PPAR-γ,increasing eNOS content and promoting NO release.

关 键 词：罗格列酮 过氧化物酶体增殖物激活受体-Γ 糖尿病 心肌肥大 一氧化氮 

分 类 号：R977.1[医药卫生—药品] R587.2[医药卫生—药学]