ERK1/2抑制剂对高糖高胰岛素诱导的肥大心肌细胞的影响作用

目的：探讨体外培养中ERK1/2抑制剂对高糖高胰岛素诱导的心肌细胞的肥大是否具有抑制作用。方法：新生Wistar大鼠心肌细胞在含有10%小牛血清的DMEM中培养72h后，换用无血清培养基并分别加入高糖高胰岛素、高糖高胰岛素+ERK1/2抑制剂培养48h，未加入任何药物的心肌细胞在无血清培养基中继续培养48h作为对照。检测心肌细胞肥大指标：心肌细胞表面积、总蛋白含量的变化；并检测心肌营养素1（CT-1）mRNA的表达。结果：高糖高胰岛素可增加心肌细胞表面积、总蛋白含量以及CT-1 mRNA表达。ERK1/2抑制剂可部分抑制心肌细胞的肥大，降低心肌细胞表面积和总蛋白含量，但对CT-1 mRNA表达的影响不明显。结论：ERK1/2抑制剂对高糖高胰岛素诱导的心肌细胞肥大具有一定的抑制作用，其作用机制可能是ERK1/2抑制剂通过作用于CT-1下游或独立于CT-1之外的信号分子而参与了高糖高胰岛素诱导心肌细胞肥大的过程。

Effect of ERK1/2 inhibitor on cardiomyocyte hypertrophy induced by high glucose and insulin in neonatal rats

Objective: To determine whether the ERK1/2 inhibitor has an inhibitory effect on cardiomyocyte hypertrophy induced by high glucose and insulin in neonatal rats.Methods: Cardiomyocytes of neonatal Wistar rats were cultured in DMEM containing 10% calf bovine serum for 72 hours,then were treated with high glucose plus high insulin or high glucose and insulin plus ERK1/2 inhibitor in serum free DMEM for another 48 hours.Cells serving as the controls were cultured in DMEM containing 10% calf bovine serum for 72 hours and then were continuously cultured in serum free DMEM for another 48 hours.Two indexes of cardiomyocyte hypertrophy were determined: the cellular surface area and the total protein content of cardiomyocytes.Expression of cardiotrophin-1(CT-1) mRNA was also determined.Results: The cellular surface area,total protein content,and CT-1 mRNA were significantly increased after treatment with high glucose and insulin compared with the controls.The ERK1/2 inhibitor partially inhibited the increased cellular surface area and the total protein content induced by high glucose and insulin,however,CT-1 mRNA expression was not affected by the ERK1/2 inhibitor in this condition.Conclusion: The ESK1/2 inhibitor might have an inhibitory effect on cardiomyocyte hypertrophy induced by high glucose and insulin,which might be because the ERK1/2 inhibitor affects the signaling molecules at the downstream of CT-1 or is independent of CT-1.