贝那普利对5／6肾切除大鼠残余肾VEGF表达及MVD变化的影响

Effect of benazepril on the VEGF and MVD in the remnant kidney of 5/6 subtotal nephrectomized rats

目的:观察血管紧张素转化酶抑制剂(angiotesin converting enzyme inhibitor,ACEI)类药物贝那普利对5/6肾切除大鼠残余肾血管内皮生长因子(vascular endothelial growth factor,VEGF)表达及微血管密度(microvessel density,MVD)的影响。方法:以SD大鼠建立5/6肾切除肾衰模型,将5/6肾切除大鼠分为模型组、贝那普利组,并设假手术组。灌药8周后取残余肾做组织病理检查,判断肾小球硬化、肾小管间质损伤程度,用免疫组织化学方法检测肾组织VEGF表达及CD141阳性MVD,并与肾小球硬化指数(glomerulosclerosis index,GSI)、肾小管间质损伤指数(tubulointerstitial score,TIS)、血清尿素氮(bloodurea nitrogen,BUN)及肌酐(creatinine,Cr)做相关分析。结果:灌药8周后贝那普利组与模型组比较,尿蛋白(urine protein,UP)、BUN和Cr明显降低,残余肾GSI和TIS明显降低(P<0.05),VEGF表达、MVD明显升高(P<0.05);肾脏VEGF表达与MVD呈显著正相关(P<0.05),肾脏VEGF表达和MVD与GSI,TIS,BUN及Cr呈显著负相关(P<0.05)。结论:5/6肾切除大鼠残余肾VEGF表达下调、MVD减少,且与残余肾纤维化密切相关;贝那普利可通过上调残余肾VEGF表达及增加MVD,从而降低CSI和TIS,缓解肾纤维化,保护肾功能。

Objective To explore the effect of benazepril （one of angiotesin converting enzymes ） on the expression of vascular endothelial growth factor （ VEGF ） and the change of microvessel density （MVD） in the remnant kidney of rats that undergone 5/6 subtotal nephrectomy （STNx）. Methods The male Sprague-Dawley （ SD ） rats were performed 5/6 nephrectomy to produce chronic renal failure, and randomly divided into a model group （STNx group ）, a STNx combined with benazepril group （Benazepril group ） , and a sham group that served as normal controls. Pathological changes of the remnant kidney were evaluated at the 8 th week after gastric gavage. Immunohistochemistry methods were used to examine the expression of VEGF and MVD in the remnant kidney, and the correlation was determined between VEGF, MVD and glomenllosclerosis index （GSI） , tubulointerstitial score （ TIS ） , BUN, and creatinine （ Cr）. Results UP, BUN, Cr, GSI, and TIS significantly decreased in the benazepirl group （ P 〈 0.05 ） ; and the expression of VEGF and MVD significant increased （ P 〈 0.05 ）. The expression of VEGF was positively related to MVD （ P 〈 0.05 ） , and there was negative correlation between VEGF, MVD and GSI, TIS, BUN, Cr （ P 〈 0.05 ）. Conclusion The decrease of the expression of VEGF and MVD in the remnant kidney may be involved in the progressive remnant kidney fibrosis and renal function, benazepril can significantly relieve the remnant kidney fibrosis and protect the renal function by increasing the expression of VEGF and MVD in the remnant kidney.