舒洛地特对糖尿病大鼠肾脏组织VEGF和VEGF-R2蛋白表达的影响

摘要

Objective: To observe the renal protection of sulodexide in diabetic rats and to investigate the mechanism. Methods: The rat models of type 1 diabetes were established by intraperitoneal injection of STZ ( streptozotocin, 65 mg/kg ). Then the rats were randomly devided into four groups: DM group ( diabetic model group ), S10 group ( 10 mg ? Kg -1 ? D -1 sulodexide group ), S20 group ( 20 mg ? Kg -1 ? D-1 sulodexide group ), L group ( losartan 30 mg ? Kg -1 ? D -1 group ), 10 rats per group. Another 10 normal rats were used as N group( normal control group ). All the rats were treated for 12 weaks. Then body weight, 24 - hour urinary albumin excretion, blood glucose ( BG ) , serum creatinine( Scr ) , blood urea nitrogen( BUN ) and kidney weight were measured; renal tissue samples were observed under optical and electron microscope. Expression of VEGF and VEGF receptor 2 ( VEGF - R2 ) in renal tissue samples was detected by Western blotting and immunohistochemistry. Results: Compared with N group, DM group had significant elevated 24 - hour urinary albumin excretion, Scr and BUN ( P < 0. 01 ), the pathological changes in the renal tissue samples in DM group were also obvious. Compared with DM group, the treated groups ( S10, S20, and L group ) had significant lower 24 -hour urinary albumin excretion( P<0.05 or P<0.01 ), but there were no significant differences of Scr and BUN among the treated groups and DM group ( P > 0.05 ). Compared with S10 group, S20 and L group had significant lower 24 - hour urinary albumin excre-tion( P <0.05 ). The pathological changes in the renal tissue samples were much ameliorated in the treated groups, especially those in the S20 and L group. The expression levels of VEGF and VEGF - R2 in DM group were significant higher than those in N group ( P <0. 01 ), and the expression levels in the treated groups were significant lower than that in DM group ( P < 0. 05 or P < 0. 01 ). Conclusion:Sulodexide has renal protective effect in diabetic rats, and 20 mg ? Kg-1 ? D-1 is more effective than 10 mg ? Kg-1 ? D . Down - regulating the renal expression of VEGF and VEGF - R2 may be one of the mechanisms through which sulodexide protects the renal tissues in diabetic rats.%目的:观察舒洛地特对糖尿病大鼠肾脏的保护作用并探讨其机制.方法:采用链脲佐霉素(STZ,60 mg/kg)腹腔注射法构建1型糖尿病大鼠模型,随机分为4组:糖尿病组(DM组)、舒洛地特10 mg·kg-1·d-1组(S10组)、舒洛地特20 mg·kg-1·d-1组(S20组)、氯沙坦30 mg·kg-1·d-1组(L组),每组各10只.另取10只未造模大鼠作正常对照组(N组).干预12周后采集各组大鼠血、尿标本和肾脏组织标本,观察和分析各组大鼠肾脏功能和结构的改变;Western blotting和免疫组织化学法检测肾组织VEGF及其受体VEGF-R2的表达.结果:同N组相比,DM组大鼠24 h尿白蛋白定量、血肌酐及尿素氮显著增加(P<0.01),病理改变较明显.同DM组相比,治疗组(S10、S20及L组)大鼠24 h尿白蛋白定量减少(P<0.05或P<0.01);同S10组相比,S20及L组大鼠24 h尿白蛋白定量减少(P<0.05).光镜及电镜显示治疗组较DM组病理变化减轻,尤以S20及L组病变减轻明显.大鼠肾脏组织VEGF和VEGF-R2的表达,DM组明显高于N组(P<0.01),治疗组显著低于DM组(P<0.05或P<0.01).结论:舒洛地特对糖尿病大鼠肾脏有保护作用,而20 mg·kg-1·d-1较10 mg·kg-1·d-1的剂量效果更好.下调肾脏组织VEGF和VEGF-R2蛋白表达可能是舒洛地特对糖尿病大鼠肾脏保护作用机制之一.