关键词: 梗阻性肾病, 去甲斑蝥素, 肾间质纤维化, wnt4, β-catenin

Abstract:

【Abstract】Objective To observe the effect of norcantharidin (NCTD) on the expression of β-catenin and Wnt4 in unilateral ureter obstructive (UUO) rats model and human proximal renal tubular epithelial cells(HK-2) fibrosis model. Methods : Firstly, sixteen male Sprague?Dawley rats were randomly divided into four groups including Sham operation group, UUO 3 days group, UUO 7 days group and UUO 14 days group (4 in each group). Secondly, another sixteen male Sprague?Dawley rats were also randomly divided into four groups: Sham operation group, UUO 14 days group, NCTD(0.05mg/kg, 0.1 mg/kg) interference group. At last, HK-2 cell were cultured and divided into control group, TGF-β1 (5ng/ml) stimulation group, TGF-β1(5ng/ml) stimulation and followed by NCTD(2.5mg/L, 5mg/L) interference group. Immunohistochemical staining, Western blotting and Real-time PCR were used to detect the protein and mRNA expression of wnt4 and β-catenin. Results With prolong of ureter obstruction time, the expression of β-catenin protein increased gradually, it was the highest level in UUO 14 days group. So we chose the rat model with UUO14 days in the following experiments, Compared with the UUO group, protein and mRNA expressions of β-catenin and Wnt4 were decreased in NTCD group, the difference is statistically significant. NTCD can also decrease the protein expression of β-catenin and Wnt4 in the HK-2 cells with TGF-β1 stimulation in the manner of concentration depedence .Conclusions NTCD can down regulate the β-catenin and Wnt4 expression in vivo and in vitro.

Key words: Obstructive nephropathy, norcanthadinrin, renal interstitial fibrosis, Wn4, β-catenin