肾康丸对糖尿病肾病大鼠TGF-β1/Smad信号通路的影响

Effect of Shenkangwan on TGF-β1/Smad signaling pathway in rat diabetic nephropathy

目的探讨肾康丸对糖尿病肾病(diabetic nephropathy,DN)大鼠TGF-β1/Smad信号通路影响。方法用链脲佐菌素(STZ)腹腔注射法诱导建立大鼠糖尿病(diabetes mellitus,DM)模型,模型成功后随机分为3组:模型对照组、开搏通组、肾康丸组,另设正常对照组,治疗8周后,取大鼠肾脏,采用逆转录聚合酶链反应(RT-PCR)法观察各组大鼠肾脏组织纤连蛋白(fibronetin,FN)和TGF-β1mRNA基因表达情况;采用免疫组化法观察各组大鼠肾脏组织Smad2、Smad3蛋白表达的情况。结果在治疗的8周里,模型组大鼠血糖均维持在16.7mmol/L以上;出现多饮、多食、多尿、消瘦的DM症状;8周后,DN模型组大鼠与正常大鼠比较,肾脏组织中FN和TGF-β1mRNA基因表达显著上调(P<0.01),Smad2、Smad3蛋白表达明显增加。肾康丸和开搏通都可以抑制DN大鼠肾脏组织中FN和TGF-β1mRNA基因表达,差异具有统计学意义(P<0.01),都可以减少Smad2、Smad3蛋白的表达。结论肾康丸可以抑制DN大鼠肾脏中TGF-β1/Smad信号转导通路的激活,减少细胞外基质合成和分泌,从而延缓DN进程。

Objective To explore the mechanism of Shenkangwan in preventing the development of diabetic nephropathy （DN） through TGF-β1/Smad signaling pathway. Methods The diabetic rat models were established by intraperitoneal injection of streptozotocin （STZ） in male Wistar rats and randomly divided into 3 groups： model control group, Capoten group and Shenkangwan group. Another 8 normal Wistar rats served as normal control. After the rats had been treated for 8 weeks, the mRNA expressions of fibronetin （FN） and TGF-β1 were detected by RT-PCR and the protein expressions of Smad 2, Smad 3 by immunohistochemistry in the renal tissues. Results During the past 8 weeks, the blood glucose of the rats in the model control group was all over 16.7 mmol/L and they exhibited the symptoms of diabetes mellitus, such as excessive thirsty, extreme hunger, frequent urination and unusual weight loss. The mRNA expressions of FN and TGF-β1 in rat renal tissues of model control group were significantly higher than those in the rats of normal control group （P 〈 0.01 ）, accompanied by the increased quantity of the cells positive of Smad 2 and Smad 3 in their kidneys. Compared with model control group, the mRNA expressions of FN and TGF-β1 as well as the protein expres- sions of Smad 2 and Smad 3 in the rat kidney tissues of Shenkangwan and capoten groups were significantly decreased （P 〈0. 01 ）. Conclusion Shenkangwan can restrain the activation of TGF-β1/Smad signaling pathway and reduce the synthesis and secretion of extracellular matrix in the renal tissues of DN rats, which would conduce to postphone the development of DN.