福辛普利与氯沙坦对实验性糖尿病大鼠肾病的防治作用与转化生长因子β_1的关系  

The effect of angitensin converting inhibitor and angiotensin Ⅱ receptor antagonist on experimental diabetic nephropathy-with transforming growth factor β_1

作　　者：王迎新[1] 李远思[2] 陈燕[2] 叶山东[2] 

机构地区：[1]安徽医学高等专科学校药理学教研室,安徽合肥230061 [2]安徽省立医院内分泌科,安徽合肥230001

出　　处：《中国药理学通报》2005年第7期884-888,共5页Chinese Pharmacological Bulletin

基　　金：安徽省自然科学基金资助项目(No01041181)

摘　　要：目的探讨转化生长因子β1(TGFβ1)与糖尿病肾病之间的关系及血管紧张素转换酶抑制剂福辛普利和血管紧张素Ⅱ受体拮抗剂氯沙坦对肾小球病变的保护作用与机制。方法建立糖尿病大鼠模型,分为正常对照(A组)、糖尿病组(B组)、福辛普利治疗组(C组)、氯沙坦治疗组(D组),检测第1、2、4、12周血糖、24h尿TGFβ1排泄率以及Alb排泄率。于第4周、第12周处死大鼠获取肾,计算肾脏肥大指数,分离皮髓质,检测肾皮质TGFβ1蛋白水平及皮质TGFβ1mRNA水平。结果①尿Alb排泄率与尿TGFβ1排泄率:各实验组尿Alb排泄率与尿TGFβ1排泄率随病程延长进一步增加,二种药物治疗均可使尿Alb排泄率与尿TGFβ1排泄率明显减少,但不能使其恢复正常。②免疫组化结果显示各实验组大鼠肾皮质TGFβ1蛋白含量较对照组显著增加,随病程延长增加更加明显,二种药物治疗组大鼠肾皮质TGFβ1蛋白含量较B组明显减少。③各时期肾皮质TGFβ1mRNA的表达量B组最高,C、D组大鼠肾皮质TGFβ1蛋白含量较B组明显减少,早期以C组减少更为明显。肾皮质TGFβ1mRNA的表达量与尿TGFβ1排泄率呈正相关。结论肾脏TGFβ1mRNA及其蛋白表达的上调可能是糖尿病肾病的发生机制之一,尿TGFβ1排泄率可以作为诊断早期糖尿病肾病和评价病变程度的标志物之一。福辛普利、氯沙坦具有确切肾脏保护作用,且福辛普利早期作用较氯沙坦更为明显。这种作用部分与其抑制肾脏TGFβ1过度表达有关。Aim ① To observe the relationship between TGFβ_1 and diabetic nephropathy in experimental rats;② To explore the effects of ACEI-fosinopril and ATRA-losartan on renal TGFβ_1 in diabetic rats and their renoprotective mechanism. Method Four groups of rats were studied, A group:normal control rats;B group: strephtozotocin induced diabetic rats;C group:diabetic rats treated with fosinopril;D group: diabetic rats treated with losartan.Blood glucose, urinary excretion rates of albumin, TGFβ_1,as well as the expressions of TGFβ_1 protein and TGFβ_1 mRNA in renal cortex and the relative kidney were measured. Result ① The urinary excretion rates of albumin and TGFβ_1 in B,C ,D groups were significant higher than those in A group, fosinopril and losartan can decrease the urinary excretion rates of the two proteins but can’t make the rate normal. ② The expressions of TGFβ_1 protein in renal cortex in B group was much higher than that in other 3 groups, fosinopril and losartan can inhibit the expression of TGFβ_1. ③ The expressions of TGFβ_1 mRNA in renal cortex increased greatest in B group, fosinopril and losartan can low the expression. Conclusion The overexpression of TGFβ_1 protein and mRNA in renal cortex of diabetic rats may be one of the mechanisms of diabetic nephropathy. Fosinopril and losartan can suppress the expressions of TGFβ_1 protein and mRNA in renal cortex, decrease the urinary excretion rates of TGFβ_1. So alleviate the patholochanges in kidney.

关 键 词：糖尿病肾病 转化生长因子Β1 尿白蛋白排泄率 血管紧张素转换酶抑制剂 血管紧张素Ⅱ受体拮抗剂 

分 类 号：R-332[医药卫生] R322.61