【摘要】 目的观察雷帕霉素(RPM)对阿霉素肾损害大鼠肾组织中血管内皮生长因子(VEGF)及其受体2(KDR)表达的影响,探讨其可能的作用机制。方法将24只雄性SD大鼠随机分为正常对照组(A组)、阿霉素肾损害组(B组)、RPM干预组(C组),每组8只。应用阿霉素(4 mg/kg)尾静脉注射、1周后重复的方法建立阿霉素肾损害大鼠模型,实验2周末给予C组RPM 1.5 mg/(kg·d)灌胃,A组和B组给予等量0.5%羧甲基纤维素。于第7周末检测各组24 h尿蛋白、血清白蛋白(Alb)、TG、TC,并观察肾组织病理形态变化,应用Western印迹法与免疫组化技术分别检测肾组织VEGF及KDR蛋白表达。结果①B组24 h尿蛋白、Alb、TG、TC明显高于A、C组(P均<0.01)。B组肾小球肥大,肾小囊扩张,肾小球有不同程度的硬化,间质可见部分纤维化和局灶性炎细胞。C组小管间质炎症和纤维化明显减轻。②C组肾组织VEGF、KDR蛋白表达明显低于B组(P均<0.01);免疫组化技术发现,B、C组肾组织VEGF受体1表达较A组增加(P均<0.05)。结论 RPM能在一定程度上减轻阿霉素肾损害大鼠慢性肾损害的发展,其机制可能与抑制VEGF、KDR蛋白表达有关。更多还原

【Abstract】 Objective To investigate the influence of rapamycin( RPM) on the expression of vascular endothelial growth factor( VEGF) and its receptor 2( KDR) in rats with adriamycin( ADR)-induced nephropathy,and to investigate the mechanism of renoprotective effect of rapamycin on the model rats. Methods Twenty-four male SD rats were randomly divided into 3 groups,8 in each group: the normal control group( group A),ADR-induced nephropathy rats group( group B) and RPM intervention group( group C). Model rats were induced by intravenous injection of ADR 4 mg / kg,and for the second injection after a week. At the end of 2 weeks after the experimentation,rats in group C were given intragastric administration of RPM 1. 5 mg( kg / d),while rats in group A and B were given the same dose of solvent. Seven weeks later, we collected specimens to detect 24 h urinary protein,serum albumin( Alb),TG and TC,and then to observe the pathological changes of renal tissues. Western blotting and immunohistochemistry techniques were used to detect VEGF and KDR protein expression in the renal tissues,respectively. Results ① 24 h urinary protein,Alb,TG and TC in group B were significantly higher than those of group A and C( all P < 0. 01). Bowman’s capsule expansion,glomeruli hypertrophy,focal fibrosis in renal tubulointerstitium and glomerulosclerosis were shown in group B,and those changes were ameliorated in group C. ②Western blotting analysis showed that the expression of VEGF and KDR in group C was significantly lower than that of group B( all P < 0. 01); immunohistochemistry showed that the expression of VEGF-R1 in renal tissues of group B and C was increased as compared with that of group A( all P < 0. 05). Conclusion RPM slows the progressive course of ADR-induced renal disease to some extent,whose mechanism may be associated with the inhibition of VEGF and KDR expression.更多还原