吡格列酮对糖尿病大鼠肾组织TGF-β1、MMP-9、Col-Ⅳ表达影响

Effects of pioglitazone on renal transforming growth factor β1,matrix metalloproteinase-9 and collagen type Ⅳ of diabetic rats

目的:探讨吡格列酮对链脲佐菌素(Streptozotocin,STZ)诱导的糖尿病大鼠肾脏保护作用及机制。方法:实验用大鼠随机分为正常对照组(Normal control,NC)、糖尿病对照组(Diabetes mellitus control,DMC)、糖尿病吡格列酮治疗组(Diabetes treat-ed with pioglitazone,DP)。DP组给予吡格列酮20 mg/(kg.d)灌胃。8周后观察大鼠血糖、尿素氮(Blood urea nitrogen,BUN)、肾指数(Kidney index,KI)、尿微量白蛋白(Microalbuminuria,MAU)等生化指标,免疫组化法观察肾组织基质金属蛋白酶9(Matrixmetalloproteinase-9,MMP-9)、转化生长因子β1(Transforming growth factorβ1,TGF-β1)及Ⅳ型胶原(Collagen typeⅣ,Col-Ⅳ)的表达。结果:DMC组大鼠BUN、KI、MAU及肾组织TGF-β1、Col-Ⅳ的表达显著高于NC组(P<0.01),而DP组BUN、KI、MAU及肾组织TGF-β1、Col-Ⅳ的表达较DMC组明显减低,差异具有显著性(P<0.01)。同时观察到DMC组MMP-9表达较NC组减低(P<0.01),而DP组较DMC组显著升高(P<0.01)。结论:吡格列酮通过下调肾组织中TGF-β1、上调MMP-9表达,对糖尿病肾病(Diabetic nephropathy,DN)起保护作用。

Objective：To study the effects of pioglitazone on diabetic nephropathy（DN）and related mechanisms.Methods：All rats were randomized into 3 groups：normal control（NC）,diabetes mellitus control（DMC）,and diabetes treated with pioglitazone（DP）.After 8 weeks of treatment,blood glucose,kidney index（KI）,microalbuminuria（MAU）,blood urea nitrogen（BUN）,and the expression of transforming growth factor β1（TGF-β1）,matrix metalloproteinase-9（MMP-9）and collagen type Ⅳ（Col-Ⅳ）in kidney were observed by immunol histochemistry.Results：KI,MAU,BUN and the expression of TGF-β1 and Col-Ⅳ in DMC group were significantly higher than other two groups（P0.01）,but the expression of MMP-9 in DMC group was significantly lower than other two groups（P0.01）.Conclusion：pioglitazone improves DN through down-regulating the expression of TGF-β1 and up-regulating MMP-9 in diabetic rats.