益肾缓衰口服液对肾大部切除大鼠残肾内VEGF表达的影响

Effect of HSR Oral Liquid on Expression of VEGP of Renal Tissue in Remnant Kidney of Subtotally Nephrectomized(SNX)Rats

目的:探讨益气养血活血的中药复方益肾缓衰口服液(HSR)对血管内皮生长因子(VEGF)在肾大部切除(SNX)大鼠残肾内表达的影响及其意义。方法:雄性Wistar大鼠76只,随机分为假手术组(n=16),模型组(n=20):5/6肾切除+自来水10ml.kg-1.d-1灌胃,益肾缓衰口服液组(n=20):5/6肾切除+HSR10ml.kg.d灌胃,氯沙坦钾(LST)组(n=20):5/6肾切除+Losartan40mg·kg-1.d-1灌胃。分别于术后2、4、8、12周采样,测血清Scr、尿蛋白定量,分别行光镜和电镜观察残肾组织病理变化;免疫组化SP法进行VEGF染色,ELISA法检测皮质部肾组织相对VEGF含量,分析VEGF表达的动态变化对肾功能和蛋白尿排泄量的影响以及与肾小球硬化指数的关系。结果:在SNX大鼠模型中,VEGF的表达随观察时间的延长而逐渐降低,与Scr、Upro的动态变化均呈负相关,r分别为:-0.59和-0.48;与肾小球硬化指数呈负相关(r=-0.73,P<0.01)。与模型组比较,缓衰方组和氯沙坦组的VEGF表达水平在整个观察周期内相对稳定,肾功能损害和病理改变相对较轻。结论:在SNX大鼠中,HSR与血管紧张素Ⅱ受体1拮抗剂(氯沙坦)具有相似的作用,均可减少蛋白尿、保护肾功能、减轻肾小球硬化,这种肾保护作用可能与其稳定残余肾内VEGF表达水平有关。

Objective：To investigate the effects of HSR oral liquid on expression of VEGF and its meaning in subtotally nephrectomized （SNX） rat. The liquid is a Chinese herbal medicinal preparation with Qi tonicity, nourishing blood and promoting blood circulation. Methods： 76 Male Wistar rats were randomly divided into four groups： （ 1 ）Sham group（ n = 16） had sham- operat- ed; （2）Model group （n = 20） were prepared by 5/6 nephrectomy （SNX） and fed with water; （3）HSR group （n = 20） SNX plus HSR oral liquid （ 10 ml·kg^-1·d^-1 ） ; （4） LST group （ n = 20） SNX plus Losartan 40 mg·kg^-1·d^-1. The rats were sacrificed after 2, 4,8,12 weeks of the treatment separately. The levels of Serum creatinine and urinary protein excretion （Upro） were tested using the routine biochemical methods. Pathological lesions of kidneys were evaluated by light microscope and electron - microscopy method. The expression of VEGF in renal cortex was detected by ELISA and immuohistochemistry. Results： VEGF expression was gradually declined in SNX group while there were no changes in HSR and Losartan Group, and there was a negative correlation between Set, Upro, Glomerulosclerosis index and the trend of VEGF（ r = - 0.59, r = - 0.48, r = - 0.73, P 〈 0.01 ）. The renal dysfunction and pathological lesions were alleviated in HSR and Losartan Groups. Conclusion： The Chinese herbal medicinal preparation HSR has sim- ilar effects as Losartan （angiotensin type 1 receptor blocker） in SNX rats, which can alleviate micmvasculature injury and renal fibrosis. The effect might be linked with expression of VEGF.