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  

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

作　　者：王松山[1] 刘真[1] 王丽红[1] 邢子英[1] 王怀经[1] 李振中[1] 

机构地区：[1]山东大学医学院解剖学教研室,山东济南250012

出　　处：《山东大学学报（医学版）》2007年第5期433-436,共4页Journal of Shandong University:Health Sciences

基　　金：山东省自然科学基金重点项目资助课题(Z2006D05)

摘　　要：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72 h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48 h,未加入任何药物的心肌细胞在无血清培养基中继续培养48 h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。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.

关 键 词：ERK1/2 葡萄糖 胰岛素 心肌肥大 大鼠 

分 类 号：R542.205[医药卫生—心血管疾病] R332[医药卫生—内科学]