舒洛地特对糖尿病大鼠肾脏病变和SOCS-1、TGF-β_1表达的影响  

Effects of Sulodexide on Nephropathy of Diabetic Rats and Expressions of SOCS1 and TGF-β_1

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9期773-776,I0003-I0004,共6页Chinese Journal of Integrated Traditional and Western Nephrology

基　　金：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STZ(链脲佐霉素,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;Western blotting和免疫组织化学法检测肾组织SOCS-1及TGF-β1蛋白的表达。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SOCS-1的表达,DM组明显高于N组(P<0.05),治疗组显著高于DM组(P<0.05或P<0.01)。大鼠肾脏组织TGF-β1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。上调肾脏组织SOCS-1的表达,抑制TGF-β1的过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. Meth- ods：The rat models of type 1 diabetes were established by intraperitoneal injection of STZ （streptozotocin, 60mg/kg）. Then the rats were randomly devided into four groups ：diabetic model group （DM group ）, 10 mg · kg-1 · d-1 sulodexide group （S10 group ） ,20 mg · kg-1 · d-1 sulodexide group（S20 group）, losartan 30 mg · kg-1 · d-1 group（L group）, 10 rats per group. Another 10 normal rats were used as normal control group（N 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 SOCS1 and TGF - 61 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 excretion （ 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 expres- sion level of SOCS1 in DM group was significant higher than that in N group （ P 〈 0.05 ）, and the expression level in the treated groups was much higher than that in DM group （P 〈0.05 or P 〈0.01 ）. The expression level of TGF - 131 in DM group was signifi- cant higher than that in N

关 键 词：舒洛地特 糖尿病肾病 细胞因子信号转导抑制因子-1 转化生子因子-β1 

分 类 号：R587.1[医药卫生—内分泌] R692.9[医药卫生—内科学]