吲哚美辛对5/6肾切除大鼠残余肾VEGF表达及MVD变化的影响

Effects of celecoxib and Indomethacin on the VEGF and Microvessel Density in remnant kidney of rats with 5/6 subtotal nephrectomy

目的观察非甾体类抗炎药（NSAIDS）吲哚美辛对5／6肾切除大鼠残余肾血管内皮生长因子（VEGF）表达、微血管密度（MVD）变化的影响。方法以SD大鼠建立5／6肾切除肾衰模型，设假手术组、模型组、吲哚美辛组。灌药8周后观察残余肾肾组织病理病变，用免疫组化法检测肾组织VEGF表达及CD141阳性微血管密度并与肾小球硬化指数（GtS）、肾间质损伤指数（TtS）、血液尿素氮（BUN）及血清肌酐（cr）做相关分析。结果灌药8周后与模型组比较，吲哚关辛组TIS显著增高、肾间质VEGF、PTC密度显著减少（P〈0．05），尿蛋白明显减轻（P〈0．05），BUN、Cr、GIS、肾小球VEGF表达、GC密度较模型组无明显变化（P〉0．05）。灌药8周后肾脏VEGF表达与MVD呈正相关（P〈0．05）。结论吲哚美辛能降低5／6肾切除大鼠尿蛋白，但可明显降低残余肾肾间质VEGF表达及PTC密度并加重小管间质的损伤程度。

Objective Our aim is to investigate the effects of Indomethacin on the expression of VEGF and the change of Mierovessel Density （MVD） in remnant kidney of rats with 5/6 subtotal nephrectomy （STNx）. Methods The renal subtotal ablation model was established by surgically 5/6 renal resection of the male Sprague-Dawley （SD） rats. Three groups were divided in our experimental protocol, including Sham, STNx and STNxI group. At the 8th week after gastric gavage, pathological changes of the remnant kidney were evaluated. Immunohistochemistry were used to examine the expression of VEGF and MVD in the remnant kidney. Results At the 8th week after gastric gavage, only Up was significant decreased （ P 〈0.05 ） . TIS in lndomethacin group was significantly increased .（ P 〈0. 05 ） and the preitubular capillary density was significant decreased（ P 〈 0. 05 ）, compared with STNx group. Although BUN, Cr, the remnant kidney glomerulusg GSI were also decreased, the difference was not statistically significant （ P 〉0.05 ）. The glomerulusg capillary density had no significant difference （ P 〉 0. 05）. In all rats, the expression of VEGF was positive correlated with capillary density between glomerulus and tabu- lointerstitium （ P 〈 0. 05）. Conclusions Indomethacin can decrease UP in remnant kidney of rats with 5/6 subtotal nephrectomy （ST- Nx）, and decrease the preitubular capillary density and aggravate tubulointerstitial injury at the same tithe.