渐尖毛蕨二氢黄酮苷对糖尿病肾病大鼠肾上皮-间质转化的影响
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篇名: 渐尖毛蕨二氢黄酮苷对糖尿病肾病大鼠肾上皮-间质转化的影响
TITLE:
摘要: 目的:考察渐尖毛蕨二氢黄酮苷(CAF)对糖尿病肾病(DKD)大鼠肾上皮-间质转化(EMT)的影响。方法:将大鼠随机分为正常组(生理盐水)、模型组(生理盐水)、阳性组[罗格列酮,0.4 mg/(kg·d)]和CAF高、低剂量组[12.5、25 mg/(kg·d)],每组10只。除正常组的其余大鼠均采用ip链脲霉素(60 mg/kg)+高脂饮食诱导DKD的发生,并于实验第13~16周同时ig相应药物。实验结束后,检测大鼠空腹血糖值和血肌酐(Scr)、尿素氮(BUN)含量,观察肾组织胶原沉积及基底膜增厚情况,免疫组化法检测肾组织中α-平滑肌肌动蛋白(α-SMA)、纤维连接蛋白(fibronectin)和上皮细胞钙黏蛋白(E-cadherin)表达,Western blot法检测肾组织中糖原合成酶激酶3β(GSK-3β)、磷酸化GSK-3β(p-GSK-3β)和β-链蛋白(β-catenin)的表达。结果:与正常组比较,模型组大鼠空腹血糖值和Scr、BUN含量均显著升高(P<0.01);肾组织有明显胶原沉积、基底膜增厚;肾组织中α-SMA、fibronectin、β-catenin表达水平和GSK-3β磷酸化程度均显著升高(P<0.01),E-cadherin表达水平显著降低(P<0.01)。与模型组比较,各给药组大鼠空腹血糖值和Scr、BUN含量均显著降低(P<0.05或P<0.01);肾组织胶原沉积和基底膜增厚情况显著改善;肾组织中α-SMA、fibronectin、β-catenin表达水平和GSK-3β磷酸化程度均显著降低(P<0.05或P<0.01),阳性组和CAF高剂量组大鼠肾组织中E-cadherin表达水平显著升高(P<0.01)。结论:CAF能抑制DKD大鼠的肾EMT,其作用的分子机制可能与下调肾组织中β-catenin表达和抑制GSK-3β磷酸化失活有关。
ABSTRACT: OBJECTIVE: To investigate the effect of Cyslosorus acuminatus flavonone glycoside (CAF) on kidney epithelial-mesenchymal transition (EMT) in rats with diabetic kidney disease (DKD). METHODS: Rats were randomly divided into normal group (normal saline), model group (normal saline), positive group [rosiglitazone, 0.4 mg/(kg·d)], CAF high-dose and low- dose groups [12.5, 25 mg/(kg·d)], 10 in each group. Except for normal group, other groups were intraperitoneally injected streptozotocin (60 mg/kg)+high fat diet to induce DKD, and intragastrically administrated related medicines in 13-16 weeks. After the experimental period, fasting blood glucose level and serum creatinine (Scr), blood urea nitrogen (BUN) contents of rats were detected, collagen deposition and basement membrane thickening in kidney tissue were observed. Immunohistochemistry was used to detect α-smooth muscle actin (α-SMA), fibronectin, epithelial cadherin (E-cadherin) expressions in kidney tissue, and Western blot was used to determine the glycogen synthase kinase 3β (GSK-3β), phosphorylated GSK-3β (p-GSK-3β), β-catenin expressions in kidney tissue. RESULTS: Compared with normal group, fasting blood glucose level, Scr and BUN contents in model group were significantly increased (P<0.01); kidney tissue showed obvious collagen deposition and basement membrane thickening;the α-SMA, fibronectin, β-catenin expression levels and GSK-3β phosphorylation degree in kidney tissue were significantly increased (P<0.01), while E-cadherin expression levels was significantly decreased (P<0.01). Compared with model group, fasting blood glucose level, Scr and BUN contents in each administration group were significantly reduced (P<0.05 or P<0.01);collagen deposition and basement membrane thickening in kidney tissue were significantly improved;the α-SMA, fibronectin, and β-catenin expression levels and GSK-3β phosphorylation degree in kidney tissue were significantly decreased (P<0.05 or P<0.01),while E-cadherin expression levels in positive group and CAF high-dose group were significantly increased (P<0.01). CONCLUSIONS: CAF can inhibit the kidney EMT of rats with DKD, the molecular mechanism may be associated with downregulating β-catenin expression and inhibiting GSK-3β phosphorylation inactivation.
期刊: 2017年第28卷第22期
作者: 熊佳俊,陈镜楼,宋红萍
AUTHORS: XIONG Jiajun,CHEN Jinglou,SONG Hongping
关键字: 渐尖毛蕨;二氢黄酮苷;糖尿病肾病;上皮-间质转化;上皮细胞钙黏蛋白;糖原合成酶激酶3β;大鼠
KEYWORDS: Cyslosorus acuminatus; Flavonone glycoside; Diabetic kidney disease; Epithelial-mesenchymal transition; Epithelial cadherin; Glycogen synthase kinase 3β; Rats
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