罗格列酮抗高糖高胰岛素诱导心肌肥大作用研究

Objective To investigate the role of rosiglitazone (RSG) in high glucose and insulin (HGI)-induced cardiac hypertrophy and its mechanisms. Methods The cardiomyocyte hypertrophy responses were assayed by measuring the cell surface area, total protein content, atrial natriuretic peptide (ANP) mRNA expression in cultured neonatal rat cardiomyocytes. Nitric oxide (NO) concentration and endothelial nitric oxide synthase (eNOS) activity were determined by using the nitrate reduction and ELISA method, respectively. The mRNA and protein expressions were detected by real-time PCR and Western blotting, respectively. Results RSG（at 0.01, 0.1, 1 μmol/L) could inhibit the HGI-induced cardiomyocyte hypertrophy in a dose-dependent way. RSG significantly increased both mRNA and protein expressions of peroxisome proliferator-activate receptor-γ (PPAR-γ), elevated mRNA expressions and enzyme activity of eNOS, and raised NO concentration in cultured media. These effects of RSG could be abolished by GW9662, a PPAR-γ inhibitor, or NG-nitro-L-arginine-methyl ester(L-NAME), a NOS inhibitor, respectively. Conclusions RSG attenuates cardiomyocyte hypertrophy induced by high glucose and insulin, and the underlying mechanisms may be by activating PPAR-γ, increasing eNOS activity, thereby promoting NO release.