益肾康对糖尿病大鼠转化生长因子β1表达的影响

Influence of Yishenkang(益肾康) on transforming growth factor β1 expression in diabetic rats

目的 :探讨益肾康对转化生长因子 β1(transforming growth factorβ1,TGFβ1)表达的影响及推测益肾康对细胞外基质 (ECM)沉积的作用。方法 :以链脲佐菌素 (STZ)制备糖尿病大鼠模型 ,随机分 4组 :正常组、模型组、达美康 +开博通组 (西药组 )、益肾康组 (中药组 )。采用免疫组化、原位杂交方法观察肾脏 TGFβ1表达和 ECM层黏蛋白 (L N)、纤维连接蛋白 (FN)、 型胶原 (Col )、 型胶原 (Col )沉积以及药物对其影响。结果 :益肾康可以降低血糖及糖化血红蛋白水平 ,明显降低蛋白尿水平 ,随着用药时间的延长 ,这种效果更加明显。西药组早期亦能降低血糖及糖化血红蛋白水平 ,但随着用药时间的延长 ,效果不如益肾康组明显。益肾康可降低肾脏肥大指数 ,与模型组比较 ,差异极显著 (P<0 .0 1) ,西药组亦能降低肾脏肥大指数 ,与模型组比较 ,差异显著 (P<0 .0 5 )。正常组 TGFβ1在肾小管上皮细胞表达微弱 ,在肾小球系膜区 TGFβ1m RNA呈弱表达 ;模型组 TGFβ1蛋白及 m RNA在肾小管上皮细胞及肾系膜表达均明显 ;而中、西药两组 TGFβ1表达较模型组为弱 (P<0 .0 1) ,西药组 TGFβ1表达较中药组明显 (P<0 .0 5 )。结论 :益肾康可能通过下调

Objective: To investigate the effect of Yishenkang(YSK,益肾康) on the expression of transforming growth factor β1(TGFβ1) and its action on the deposition in the extracellular matrix(ECM).Methods: The rats were randomly divided into four groups: normal group, model group, YSK group(traditional Chinese medicine group), captopril and damilke group(western medicine group). The diabetic rats model was made by injection streptozotocin(STZ) 55 mg/kg from tail vein. The change of the kidney hypertrophy exponent (kidney weight/body weight), plasma glucose, glycated hemoglobin(Hb), urinary albumin and the expression of laminin (LN), fibronectin (FN), collagen type Ⅲ(Col Ⅲ), collagen type Ⅳ(Col Ⅳ) were measured with immunohistochemistry and in situ hybridization analyses, and the effect of medicine was observed . Results: The YSK could decrease the level of plasma glucose, glycated Hb, urinary albumin obviously, as the time went on, the effect was more significantly. The western medicine could also decrease the level of plasma glucose and glycated Hb significantly at the early days, but as the time went on, the effect was not stable as the YSK. YSK and western medicine all could reduce the kidney hypertrophy expotent, the difference was significant compared to that of the model group (both P<0 01). The expression of TGFβ1 was faint at renal tubules epithelium cell and the expression of TGFβ1 mRNA was weak at glomerular mesangial of the normal group. The expression of TGFβ1 protein and mRNA at renal tubules epithelium cell, and glomerular mesangial cells were both obvious in the model group. The expression of TGFβ1 in the two treatment groups were weaker than the model group (P<0 01). The expression of TGFβ1 was significantly increased in western medicine group than the traditional Chinese medicine group (P<0 05). Conclusion: YSK can decrease the deposition of the glomerular ECM, perhaps by downregulating the expression of TGFβ1.