中介素对单侧输尿管梗阻大鼠模型微血管损伤的影响

Effect of intermedin on microvascular injury of unilateral ureteral obstruction rats

目的研究中介素（intermedin，IMD）在单侧输尿管梗阻（UUO）大鼠模型肾脏纤维化进展中对微血管损伤的影响。方法雄性Wistar大鼠72只，随机分为假手术组（n=24，行左输尿管分离术）、模型组（UUO，n=24）和IMD组（n=24），后两组行左输尿管结扎术。各组大鼠分别在术后7d、14d、21d、28d各取6只，留取血液及梗阻侧肾组织标本。用HE、Masson染色观察肾组织病理变化；用全自动生化分析仪检测血尿素氮（BUN）、血肌酐（Scr）及胱抑素C（CysC）含量；用RT-PCR法检测肾组织转化生长因子β1（TGF-β1）、仅平滑肌肌动蛋白（α-SMA）、骨形态发生蛋白7（BMP-7）、E钙黏蛋白（E-cadhefin）、血小板反应蛋白1（TSP-1）及血管内皮生长因子（VEGF）的mRNA表达，以免疫组化法检测其蛋白的表达，并进行半定量分析。结果与假手术组相比，不同时间点UUO组大鼠肾组织纤维化程度明显，小管间质损害加重，血BUN、Scr、CysC升高（P〈0．05），TGF-β1、α-SMA、TSP-1 mRNA及蛋白表达量增多（P〈0．05），BMP-7、E—cadherin及VEGF减少（P〈0．05）；与UUO组相比，IMD组肾小管损害、间质纤维化程度均较轻，血BUN、Scr、CysC降低（P〈0．05），TGF-β1、α—SMA、TSP－1mRNA及蛋白表达量减少（P〈0．05），BMP-7、E—cadhefin及VEGF增多（P〈0．05）。结论中介素在肾脏纤维化进程中可保护。肾功能，减轻纤维化，可能与介导VEGF减轻血管损伤有关。

Objective To observe the effect of intermedin（IMD） on microvascular injury of renal fibrosis in unilateral ureteral obstruction （UUO） rat model. Methods Seventy-two male Wistar rats were randomly divided into two groups： the sham-operation group （n=24） underwent the left ureteral dissection, the other 48 rats were made as unilateral ureteral obstruction models and subdivided into model group（UUO, n=24） and IMD group （n=24）. At the 7, 14, 21, 28 day after the operation, 6 randomly-selected rats from each of the three groups respectively were blooded by abdominal arotic and their obstructive kidneys were taken out. The renal histopathological changes were observed through HE and Masson staining, the contents of BUN, Scr and cystatin C （CysC） of the obstructive kidneys were determined, the expressions of transforming growth factor-β1 （TGF-β1）, α-SMA, bone morphogenetic protein-7 （BMP-7）, E-cadherin, thrombospondin 1 （TSP-1） and vascular endothelial growth factor （VEGF） were detected by RT- PCR and immunohistochemistry. Results Compared with the sham-operated group, the pathological changes of kidney in the model group showed that the degree of fibrosis was obvious, tubular interstitial damage aggravated, the levels of BUN, Scr, CysC in the model group increased （P 〈 0.05）, the mRNA expression and protein content of TGF-β1, α-SMA, TSP-1 increased （P 〈 0.05）, while the levels of BMP-7, E-cadherin and VEGF decreased （P 〈 0.05）. Compared with the UUO group, renal tubular damage, interstitial fibrosis in the IMD group were lighter, the levels of BUN, Scr, CysC in the IMD group were lower （P 〈 0.05）, the mRNA expression and protein content of TGF - β1, α- SMA,TSP- 1 were down-regulated （P 〈 0.05）, while the levels of BMP-7, E-cadherin and VEGF were up-regulated （P 〈 0.05）. Conclusion IMD can ameliorate the renal interstitial fibrosis, and the mechanism may be related to the fact that VEGF mediated by IMD can reduce vascular injury.