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  

The Effects of Sulodexide on Expression of VEGF and VEGF-R2 in Renal Tissue with Diabetic Nephropathy

作　　者：杨绪枫[1] 王筱霞[1] 汪年松[1] 王锋[1] 田寿福[1] 陈玉强[1] 李青[2] 陈海冰[2] 

机构地区：[1]上海交通大学附属第六人民医院肾脏内科,上海200233 [2]上海交通大学附属第六人民医院内分泌科,上海市糖尿病临床医学中心,上海市糖尿病研究所,上海200233

出　　处：《中国中西医结合肾病杂志》2012年第11期948-951,I0001,共5页Chinese Journal of Integrated Traditional and Western Nephrology

基　　金：上海市国际科技合作基金资助项目(No.11410708500);上海市科委基金资助项目(No.114119a6100);上海市级医院新兴前沿技术攻关项目(No.SHDC12006101);阿尔法韦士曼(北京)市场策划管理有限公司科研基金资助项目

摘　　要：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,60mg/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10mg·kg-1·d-1组(S10组)、舒洛地特20mg·kg-1·d-1组(S20组)、氯沙坦30mg·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;Westernblot-ting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24h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24h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24h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20mg·kg-1·d-1较10mg·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。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 （P0.01）,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（P0.05 or P0.01）,but there were no significant differences of Scr and BUN among the treated groups and DM group （P0.05）.Compared with S10 group,S20 and L group had significant lower 24-hour urinary albumin excretion（P0.05）.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（P0.01）,and the expression levels in the treated groups were significant lower than that in DM group （P0.05 or P0.01）.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-1.Down-regulating the ren

关 键 词：舒洛地特 糖尿病肾病 血管内皮细胞生长因子 血管内皮细胞生长因子受体 

分 类 号：R587.1[医药卫生—内分泌]