伊马替尼对尿毒症心肌病大鼠心肌纤维化的保护作用

摘要

Objective To evaluate the effect of imatinib in improving myocardial fibrosis in uremic rats through regulating the expression of PDGFRα.Methods Seventy two rats were divided into three groups ,which were Sham group ,5/6 group and 5/6+I group .All The rats in 5/6 group underwent the 5/6 nephrectomy and the rats in 5/6+I group were given imatinib by ga‐vage after the operation of 5/6 nephrectomy .Hearts were harvested for HE and Sirius red staining at 8 weeks post surgery .The ex‐pression of PDGFRαwas assessed with immunohistological staining .The real‐time PCR was employed to detect the PDGFRαmR‐NA level in hear samples .Results The urine protein ,Scr ,BUN of the 5/6 group and 5/6+I group were higher than that of Sham group(P<0 .01) .The myocardial pathological score in Sham group was significantly lower than that of 5/6 group (P<0 .01) ,and the score in 5/6+I group was significantly lower than that of 5/6 group (P<0 .01) .The collagen volume fraction (CVF) in 5/6 group was significantly higher than that in Sham group (P<0 .01) .And the CVF in 5/6+ I group was higher than that in Sham group (P<0 .05) ,but lower than that of 5/6 group (P<0 .05) .The expression ratio of PDGFRαmRNA and staining rate in 5/6 group and 5/6+I group were both much higher than that in Sham group (P<0 .01) ,and the expression in 5/6+I group was signif‐icantly lower than that in 5/6 group (P<0 .05) .Conclusion These data suggest that the tyrosine kinase inhibitor imatinib reduces heart injury and attenuates myocardial fibrosis in uremic rat by mechanisms associated with the inhibition of the expression of PDGFRα.%目的：观察伊马替尼通过调控 PDGFRα的表达改善尿毒症大鼠心肌纤维化的作用。方法将72只大鼠分为Sham组，5／6组和5／6＋I组，5／6组建立大鼠尿毒症模型，5／6＋I组建模后行伊马替尼灌胃，Sham组仅行肾脏游离。所有大鼠于术后8周行心脏病理染色；实时定量荧光PCR、免疫组织化学测定心脏血小板衍生生长因子受体α（PDGFRα） mRNA及蛋白表达。结果5／6组和5／6＋I组大鼠尿蛋白、Scr、BUN均较Sham组明显增加（P＜0．01）．Sham组心肌病理评分显著低于5／6组（P＜0．01），而5／6＋I组显著低于5／6组（P＜0．01）；5／6组心肌间质胶原容积分数值明显高于Sham组（P＜0．01）；5／6＋ I组高于Sham组（P＜0．05），但与5／6组比较，明显下降（P＜0．05）；5／6组和5／6＋ I组的 PDGFRα mRNA 和蛋白表达均显著高于Sham组（均 P＜0．01）；而5／6＋I组明显低于5／6组（P＜0．05）。结论伊马替尼可以通过抑制PDGFRα表达减少尿毒症大鼠心脏病理损伤及纤维化的程度。