Chang Bao-Chao, Chen Wei-Dong, Zhang Yan, Yang Ping, Liu Lei, Wang Jing
Zhongguo Zhong Yao Za Zhi. 2014 Oct;39(19):3829-35.
The study is to explore the effect of total glucosides of paeony (TGP)on Wnt/β-catenin signal transduction pathway expression in kidney of diabetic rats, and discuss the protection of TGP in diabetic nephropathy and possible mechanism. Ninety male SD rats of 8 weeks age were randomly divided into normal control group (n = 10) and model group (n = 80). Rats of the normal control group were fed with regular diet, while rats of the model group were fed with high-fat high-sugar diet and 4 weeks later were given an intraperitoneal injection of 35 mg x kg(-1) streptozotocin (STZ). The successfully induced type 2 diabetic rat models were then randomly divided into DM group, three TGP (50, 100, 200 mg x kg(-1) x d(-1)) treatment group and tripterygium wilfordii glycosides (8 mg x kg(-1) x d(-1)) control group. Rats of DM group and each treatment group were given high-fat high-sugar diet. At week 14, the levels of blood sugar, 24 hour urine protein, serum creatinine and blood urea nitrogen were tested. The rats were then sacrificed. Renal pathological changes were examined. Renal tissue Wnt-1 and β-catenin expressions were detected by immunohistochemical assay. Wnt-1 mRNA and β-catenin mRNA expression was semi-quantified by RT-PCR. Wnt-1 protein and β-catenin protein expression was semi-quantified by Western blot. The Result show that Wnt-1 and β-catenin expression increased in kidney of high-fat high-sugar induced type 2 diabetic rats. Compared with diabetic group, the level of serum creatinine, blood urea nitrogen, 24 h urine protein, mean glomerular area and mean glomerular volume were decreased, renal histopathology were improved, expression of Wnt-1 and β-catenin mRNA and protein was reduced in TGP group. Tripterygium wilfordii glycosides had the similar effect. In conclusion, these results showed that Wnt/β-catenin abnormal activation in kidney of type 2 diabetic rats, TGP can improve kidney damage in diabetic rats and delay the development of diabetic nephropathy by inhibit the Wnt/β-catenin signaling pathway.
本研究旨在探讨芍药总苷（TGP）对糖尿病大鼠肾脏Wnt/β-连环蛋白信号转导通路表达的影响，并探讨TGP对糖尿病肾病的保护作用及可能机制。将90只8周龄雄性SD大鼠随机分为正常对照组（n = 10）和模型组（n = 80）。正常对照组大鼠给予常规饮食，模型组大鼠给予高脂高糖饮食，4周后腹腔注射35 mg·kg⁻¹链脲佐菌素（STZ）。将成功诱导的2型糖尿病大鼠模型随机分为糖尿病组、3个TGP（50、100、200 mg·kg⁻¹·d⁻¹）治疗组和雷公藤多苷（8 mg·kg⁻¹·d⁻¹）对照组。糖尿病组和各治疗组大鼠给予高脂高糖饮食。在第14周时，检测血糖、24小时尿蛋白、血清肌酐和血尿素氮水平。然后处死大鼠，检查肾脏病理变化。采用免疫组织化学法检测肾组织Wnt-1和β-连环蛋白表达。采用RT-PCR对Wnt-1 mRNA和β-连环蛋白mRNA表达进行半定量分析。采用Western blot对Wnt-1蛋白和β-连环蛋白蛋白表达进行半定量分析。结果显示，高脂高糖诱导的2型糖尿病大鼠肾脏中Wnt-1和β-连环蛋白表达增加。与糖尿病组相比，TGP组血清肌酐、血尿素氮、24小时尿蛋白水平、平均肾小球面积和平均肾小球体积降低，肾脏组织病理学得到改善，Wnt-1和β-连环蛋白mRNA及蛋白表达降低。雷公藤多苷有类似作用。综上所述，这些结果表明2型糖尿病大鼠肾脏中Wnt/β-连环蛋白异常激活，TGP可通过抑制Wnt/β-连环蛋白信号通路改善糖尿病大鼠肾脏损伤并延缓糖尿病肾病的发展。
