桃红四物汤改善糖尿病肾病大鼠肾脏纤维化的作用机制研究

Mechanism of Taohong Siwu Decoction improves renal fibrosis in diabetic nephropathy rats

目的 探讨桃红四物汤对糖尿病肾病(DN)大鼠肾脏纤维化及JAK2-STAT3信号通路的影响。方法 50只SPF级SD大鼠,随机分为正常对照组、模型组、桃红四物汤高、中、低剂量组,每组10只,采用高糖高脂喂饲联合腹腔注射链脲佐菌素的方法复制DN大鼠模型,测定空腹血糖水平;24 h尿蛋白量(UPro)和血尿素氮(BUN)、血清肌酐(SCr)水平;HE染色观察大鼠肾脏病理损伤;Masson染色观察大鼠肾脏纤维化程度;Western blot法测定肾脏胶原蛋白I(Col-I)、Col-III、纤连蛋白(FN)、Janus蛋白激酶2(JAK2)、信号转导和转录激活因子3(STAT3)、磷酸化JAK2(p-JAK2)、p-STAT3。结果 与模型组相比,桃红四物汤中、高剂量组空腹血糖、UPro和BUN、SCr水平均显著降低,肾脏病理性结构和纤维化明显改善,肾脏Col I、Col III、FN蛋白表达显著降低,并且p-JAK2/JAK2、p-STAT3/STAT3比值显著降低(P<0.05)。结论 桃红四物汤可能是通过抑制JAK2-STAT3信号通路发挥延缓糖尿病肾病大鼠肾脏纤维化的作用。

Objective To investigate the effects of Taohong Siwu Decoction on renal fibrosis and JAK2-STAT3 signaling pathway in diabetic nephropathy(DN)rats.Methods Fifty SD rats were randomly divided into control group,model group,high,middle and low dose Taohong Siwu decoction groups,with 10 rats in each group.DN rat model was established by feeding with high glucose and high fat and intraperitoneal injection of streptozotocin.Fasting blood glucose was measured.Levels of urinary protein(UPro),blood urea nitrogen(BUN)and serum creatinine(SCr)at 24 h were measured.Renal pathological injury was observed by HE staining.The degree of renal fibrosis was observed by Masson staining.The expressions of Collagen I(Col-I),Col-III,fibronectin(FN),Janus kinase 2(JAK2),signal transduction and transcriptional activator 3(STAT3),phosphorylated JAK2(p-JAK2)and p-STAT3 were determined by Western blot.Results Compared with model group,the fasting blood glucose level,the levels of UPro,BUN and SCr were significantly decreased in Taohong Siwu decoction medium and high dose groups,the renal pathological structure and fibrosis were significantly improved,and the expressions of Col I,Col III and FN protein were significantly decreased.p-JAK2/JAK2 and p-STAT3/STAT3 ratios were significantly decreased(P<0.05).Conclusion Taohong Siwu decoction may delay renal fibrosis in diabetic nephropathy rats by inhibiting JAK2-STAT3 signaling pathway.