羟苯磺酸钙对5／6肾切除大鼠肾脏微血管的保护机制

Effects of Calcium dobesilate on renal microvasculature injury in 5/6 subtotal nephrectomy rats model

目的探讨羟苯磺酸钙对5／6肾切除大鼠肾脏微血管的保护作用及其机制。方法复制5／6肾切除大鼠模型，设5／6肾切除模型组和羟苯磺酸钙干预组，在二次手术后第1、2、4、8、12周观察各组大鼠肾功能及残肾组织病理改变。采用免疫组化观察肾脏Ang-1和CD31表达的变化，RT-PCR观察肾脏Ang-1 mRNA的表达并行相关性分析。结果与同时点模型组比较，羟苯磺酸钙干预组大鼠尿蛋白减少、肾功能改善、残肾组织病理改变明显减轻。自第2周开始Ang-1 mRNA及蛋白表达水平升高，其后期的下调趋势变缓、CD31表达增强、肾脏微血管病变显著改善。结论羟苯磺酸钙可能通过增强Ang-1早期的上调幅度并延缓后期的下调来改善5／6。肾切除大鼠肾脏的微血管病变，从而保护肾脏。

Objective To observe and probe into the effects and mechanism of action of calcium dobesilate on the renal mierovasculature injury in the remnant kidneys of rats with 5/6 nephrectomy. Methods Rat model were established in adult male SD rats by 5/6 nephrectomy. The rats were randomly divided into model and calcium dobesilate intervention group. The renal function and histopathological changes were evaluated at 1, 2, 4, 8 and 12 weeks after operation finished. The expressions of Ang-1 and CD31 in renal were detected by immunohistochemistry. Ang-1 mRNA was detected by RT-PCR at the same time-points. The levels of Ang-1 and CD31 were quantified by computer image analysis. Results In calcium dobesilate intervention group, urine protein decreased,the renal function improved and the pathological changes of remnant kidney lessen significantly as compared with the model group at the same time-points. Except at 1 w, the expression of Ang-1 and CD31 in the intervention group was higher than that in the subtotal nephrectomy group at the other time points, and the difference between the groups was significant （P〈0. 05, P〈0. 01 ）. Conclusions Calcium dobesilate may protect kidney by increasing the content of angiopoietin-1 to improve the renal microvasculature injury in the remnant kidney.