脂联素抑制高浓度胰岛素诱导的大鼠心肌细胞肥大

Adiponectin inhibits cardiomyocyte hypertrophy induced by high concentration of insulin in rats

目的探讨脂联素(APN)是否通过上调AdipoR1/AMPK/PI3K/AKT抑制高浓度胰岛素诱导的大鼠心肌细胞肥大。方法分离新生SD大鼠心肌细胞并连续培养9 d,按干预条件不同将心肌细胞分为4组:对照组(培养基)、模型组(1×10-6mol/L胰岛素)、干预组(1×10-6mol/L胰岛素+7.5mg/L脂联素)和转染组(AdipoR1 siRNA转染后胰岛素+脂联素处理)。48 h后检测各组心肌细胞的平均蛋白含量、3-甲基组氨酸(3-MH)含量及心肌细胞表面积;Western blot检测脂联素受体1(AdipoR1)、腺苷酸活化蛋白激酶(AMPK)、磷脂酰肌醇3-激酶(PI3K)和蛋白激酶B(AKT)蛋白的表达。结果与对照组相比,模型组心肌细胞平均蛋白含量增多(P<0.05)、3-MH含量减少(P<0.05)及心肌细胞相对表面积增大(P<0.01);与模型组相比,干预组上述变化显著减轻,干预组AdipoR1、AMPK、PI3K和AKT蛋白表达量增加(P<0.05)。结论脂联素可通过上调AdipoR1/AMPK/PI3K/AKT抑制高浓度胰岛素诱导的大鼠心肌细胞肥大。

Objective To investigate whether adiponectin（ APN） inhibits cardiomyocyte hypertrophy induced by high concentration of insulin through up-regulating AdipoR1/AMPK/PI3 K/AKT. Methods The cardiomyocytes of neonatal SD rats were isolated and continuously cultured for 9 days. Cardiomyocytes were divided into 4 groups according to different intervention conditions： control group（ medium）,model group（ 1×10-6 mol/L insulin）,intervention group（ 1×10-6 mol/L insulin＋7. 5 mg/L adiponectin） and transfection group（ AdipoR1 siRNA insulin＋adiponectin processing after transfection）. After 48 hours,the average protein content,3-methylhistidine（ 3-MH）content and myocardial cell surface area of each group were detected. Western blot was used to detect the expressionof AdipoR1,AMPK,PI3 K and AKT proteins. Results The average protein content of myocardial cells increased（ P〈0. 05） and the content of 3-MH decreased（ P〈0. 05）. Compared with the model group,the above changes in the intervention group were significantly reduced,while the expression of AdipoR1,AMPK,PI3 K and AKT in the intervention group was increased（ P〈0. 05）. Conclusions Adiponectin may inhibit rat cardiomyocyte hypertrophy induced by high concentration of insulin through up-regulating AdipoR1/AMPK/PI3 K/AKT.