过氧化物酶体增殖物激活受体γ激动剂对直流电刺激后兔缺血心肌组织中PTEN蛋白表达及左室重构的影响

Peroxisome proliferator-activated receptor gamma agonist promotes PTEN expression and left ventricular remodeling in rabbit ischemia myocardium

目的探讨染色体10缺失的磷酸酶与张力蛋白同源物基因（PTEN）在兔急性心肌梗死（MI）边缘区心肌组织中的表达及其意义以及过氧化物酶体增殖物激活受体（PPAR）γ激动剂（罗格列酮）对其表达的影响。方法50只日本大耳白兔，随机分为假手术组（SH组，n=5）、MI组n=15、常规电刺激组（EFs组，n=15）和罗格列酮干预电刺激组（R．EFs组，n=15）。结扎冠状动脉左前降支建立急性MI或SH组模型后，在结扎血管两侧心外膜上缝合固定一对铂金电极，直流电刺激（电场强度4．0V／cm，30min／d），罗格列酮以4mg／（kg·d）灌胃。实验终点以Western印迹法检测各组1周、2周及4周时心肌组织中PTEN表达并测定左、右心室重量和血流动力学指标。结果正常心肌组织和缺血心肌组织均有一定程度PTEN表达，EFs组心肌组织中PTEN表达较MI组升高（P〈0．01），罗格列酮干预使缺血心肌组织中PTEN表达较EFs组进一步升高（P〈0．05），同时左室收缩功能较EFs组进一步改善。结论PPARy激动剂可进一步促进缺血心肌组织在直流电刺激后PTEN的表达，从而使左心室功能得到改善。

Objective To determine the expression and significance of phosphatase and tensin homologue deleted on chromosome 10 （PTEN） in the marginal area of myocardial infarction, and the effect of peroxisome proliferator-activated receptor gamma agonist （PPAR-γ）, rosiglitazone, on the expression in acute myocardial infarction （MI） rabbit model after the direct current （DC） electric fields （EFs） stimulation. Methods Fifty rabbits were randomly divided into sham-operation group （SH group, n = 5）, MI group （n = 15）, DCEFs treatment group （EFs group, n = 15）, and DCEFs＋rosiglitazone treatment group （R-EFs group, rosiglitazone 4 mg/kg · d, i.g.）. After the corresponding model was established by occluding left anterior descending branch in the later 3 groups, DCEFs stimulation （4.0V/cm, 30min/d） was given to the later 2 groups for 1, 2 and 4 weeks respectively （n = 5 for each time point）. The expression of PTEN in the ischemia myocardium was detected by Western blotting. Meanwhile, the ratio of left or right ventricular weight/body mass （LVW/BS or RVW/BS） and the hemodynamic indexes were measured. Results There was some expression of PTEN in cardiac tissue of SH group and MI group. The expression of PTEN in EFs group was higher than in MI group（P 〈 0.01）, and the expression in R-EFs group was higher than EFs group（P 〈 0.05）. In the meantime, compared to MI group, left ventricular function was improved in EFs group and R-EFs group. Conclusion PPARγ promotes the expression of PTEN and thus further improves the left ventricular systolic function.