中介素对大鼠单侧输尿管梗阻模型肾小球血管内皮间充质转分化的影响

Effect of intermedin on glomerular endothelial-to-mesenchymal transition in rats with unilateral ureteral obstruction

目的观察中介素(IMD)对单侧输尿管梗阻(UUO)大鼠模型肾小球血管内皮细胞间充质转分化的影响。方法雄性Wistar大鼠72只,分为假手术组24只、UUO 24只和IMD组24只。各组大鼠分别于术后7、14、21和28 d随机选取6只,留取梗阻侧肾组织;免疫组织化学法检测血小板内皮细胞黏附分子CD31、氨肽酶P(JG-l2)、血管内皮生长因子(VEGF)、VEGF受体-2(VEGFR2)、血管内皮钙黏蛋白(VE-cadherin)、α-平滑肌肌动蛋白(SMA)、转化生长因子(TGF)-β_2、骨形态发生蛋白质(BMP)-7表达;实时荧光定量聚合酶链反应(RTPCR)法检测上述相关因子m RNA表达并进行半定量分析。结果与假手术组相比不同时间点各组大鼠TGF-β_2、α-SMA相对表达量及蛋白含量增多(P<0.05),CD31、JG-12、BMP-7、VE-cadherin及VEGF、VEGFR2减少(P<0.05);与UUO组相比,IMD组TGF-β_2、α-SMA m RNA相对表达量及蛋白含量减少(P<0.05),CD31、JG-12、BMP-7、VE-cadherin及VEGF、VEGFR2增多(P<0.05)。结论 IMD在肾脏纤维化进程中可保护肾功能,减轻肾小球纤维化,与抑制肾小球血管内皮细胞间充质转分化有关。

Objective To investigate the effect of intermedin（IMD） on glomerular endothelial-to-mesenchymal transition（Endo MT） in rats with unilateral ureteral obstruction（UUO）. Methods Seventy-two male Wistar rats were randomly divided into the sham operation group（n =24）, UUO model group（n =24） and IMD group（n =24）. Six rats from each group were randomly included at 7, 14, 21 and 28 days, and the obstructed kidney tissues were reserved.Immunohistochemistry was used to determine the expression of platelet endothelial cell adhesion molecule（PECAM）CD31, aminopeptidase P（JG-l2）, vascular endothelial growth factor（VEGF）, VEGF receptor-2（VEGFR2）, vascular endothelial-cadherin（VE-cadherin）, α-smooth muscle actin（α-SMA）, transforming growth factor-β_2（TGF-β_2）, and bone morphogenetic protein（BMP）-7. The m RNA expression of the correlation factors was examined by real-time polymerase chain reaction（RT-PCR） for semi-quantitative analysis. Results Compared with the sham operation group,the m RNA relative expression and protein content of TGF-β_2and α-SMA at different time points were increased（P〈0.05）, whereas the m RNA relative expression and protein content of CD31, JG-12, BMP-7, VE-cadherin, VEGF and VEGFR2 were decreased（P〈0.05） in the UUO group and IMD group. Compared with UUO group, the m RNA relative expression and protein content of TGF-β_2and α-SMA were decreased（P〈0.05）, and the m RNA relative expression and protein content of CD31, JG-12, BMP-7, VE-cadherin, VEGF and VEGFR2 were increased（P〈0.05）in the IMD group. Conclusion IMD can protect renal function and reduce glomerular fibrosis, related to inhibited glomerular Endo MT.