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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 myocardial hypertrophy induced by high glucose and insulin (HGI) and its mechanism. Methods Cardiomyocytes were cultured with HGI to establish cardiomyocyte hypertrophy model and treated with different concentrations of RSG. The cell surface area, protein content and the mRNA level of ANP gene were determined as myocardial hypertrophy The effects of RSG on HGI-induced cardiac hypertrophy were observed. Real-time PCR and Western blot were used to detect the expression of peroxisome proliferator-activated receptor-γ (PPAR-γ) The mRNA and protein levels of eNOS and eNOS were detected by ABC-ELISA and nitrate reduction respectively. Results HGI induced hypertrophy in rat cardiomyocytes. RSG inhibited HGI-induced cardiomyocyte hypertrophy in a concentration-dependent manner and significantly increased the mRNA and protein levels of PPAR-γ and eNOS induced by HGI and increased the expression of PPAR-γ protein Level, eNOS and NO content (all P <0.05). Both the PPAR-γ inhibitor GW9662 and the NOS inhibitor L- nitro-arginine methyl ester (L-NAME) can block the above effects of RSG. Conclusion RSG can inhibit HGI-induced cardiomyocyte hypertrophy by activating PPAR-γ receptor, increasing eNOS content and promoting NO release.