吡格列酮对培养的心肌细胞肥大的抑制作用

目的: 利用体外培养的乳鼠心肌细胞, 观察吡格列酮对高浓度葡萄糖与去甲肾上腺素共同诱导的肥大心肌细胞的影响, 进一步推测吡格列酮对糖尿病性心肌肥大的可能作用及作用机制。方法: 以培养的乳鼠心肌细胞为模型分组给药后, 用显微镜目镜计数心肌细胞搏动的频率;用Lowry' s 法测心肌细胞的蛋白质含量;用³H] leucine 标记法测定心肌细胞蛋白的合成;利用计算机图象分析系统测心肌细胞的体积。结果: 吡格列酮在1 ～ 10 μmol·L^-1 浓度对25. 5 mmol·L^-1高糖与1 μmol·L^-1去甲肾上腺素联合诱导的肥大心肌细胞的蛋白含量、蛋白合成及体积均有显著的抑制作用。其抑制肥大的效果比1 μmol·L^-1 维拉帕米更为显著;同时观察到10 μmol·L^-1吡格列酮同1 μmol·L^-1维拉帕米一样有抑制心肌细胞搏动的作用。结论: 吡格列酮能有效抑制高糖与去甲肾上腺素联合诱导的心肌细胞肥大。这种作用可能是通过作用于PPARγ来实现的。

Inhibitory effect of pioglitazone on hypertrophy of cultured neonatal rat ventricular myocytes induced by high glucose and norepinephrine

AIM: To study the inhibitory effect of pioglitazone on cultured hypertrophic ventricular myocyte induced by high glucose and norepinephrine (NE ).METHODS: Using cultured ventricular myocytes as a model, the protein contentss was assayed with Lowry' s method, the protein synthesis was assayed with ³H] leucine intake method, the cardiomyocytes' volumes were measured by computer photograph analysis system, and the cellular hypertrophy was observed. The contracting frequency was counted by the inverted microscope.RESULTS: Compared with 1 μmol·L^-1 verapamil, pioglitazone at the concentration of 1-10 μmol·L^-1 inhibited the protein contents, cellular protein synthesis and volumes of the ventricular myocytes in a dose dependent manner. Meanwhile, 10 μmol·L^-1 pioglitazone and 1 μmol·L^-1 verapamil inhibited cellular contracting f requency too.CONCLUSION: Pioglitazone at the concentration of 1-10 μmol·L^-1 can effectively inhibit hypertrophy of cultured ventricular myocytes induced by high glucose and NE.