加味六味地黄汤对UUO大鼠肾组织Wnt4/β-catenin信号通路介导调控FGF-23的影响  

The Effect of Jiaweiliuweidihuang Decoction on the Regulation of Wnt4/β-catenin Pathway Mediated Fibroblast Growth Factor-23 in the Rat’s Kidney with Unilateral Ureteral Obstruction

作　　者：黄仁发 梁群卿[2] 邓鸣 刘学耀 杨义龙 黄家晟 陈鹏辉 吴金玉[3] HUANG Renfa;LIANG Qunqing;DENG Ming(Nephrology Department,the Shenzhen Hospital(Futian) of Guangzhou University of Traditional Chinese Medicine,Shenzhen,518034)

机构地区：[1]广州中医药大学深圳医院(福田)肾内科,深圳518034 [2]广西中医药大学附属瑞康医院健康体检中心,南宁530011 [3]广西中医药大学第一附属医院肾内科,南宁530023

出　　处：《中国中西医结合肾病杂志》2019年第4期285-289,共5页Chinese Journal of Integrated Traditional and Western Nephrology

基　　金：国家自然科学基金(No.81760805,81460682,81760805);广西自然科学基金课题(No.2015GXNSFAA139134)

摘　　要：目的:观察加味六味地黄汤对单侧输尿管梗阻(UUO)大鼠肾组Wnt4、β-catenin及FGF-23蛋白表达的影响。方法:健康成年SD大鼠120只,随机分为4组:假手术组、模型组、中药组、缬沙坦组,各组组内分为1周、2周、4周3个时间点。假手术组和模型组予以生理盐水(2 ml/只/d)灌胃;中药组予以加味六味地黄汤组灌胃(2 ml/d);缬沙坦组在造模后给予缬沙坦(30 mg·kg^-1·d^-1)灌胃。HE染色和Masson染色观察肾脏病理改变,免疫组化和Western blot观察大鼠肾组织Wnt4、β-catenin及FGF-23蛋白的表达。结果:假手术组大鼠肾组织结构正常,模型组大鼠出现肾间质纤维化,中药组和缬沙坦组大鼠小管间质病变减轻。与假手术组相同时间点相比较,大鼠模型组肾功能(BUN、Scr)、小管间质半定量评分、Wnt4、β-catenin及FGF-23蛋白表达均显著增高,差异均有统计学意义(P<0.01);与模型组大鼠相同时间点相比较,加味六味地黄汤和缬沙坦均能改善肾脏病理,显著降低BUN和Scr水平、小管间质半定量评分,下调肾组织Wnt4、β-catenin及FGF-23蛋白的表达(P<0.05或P<0.01)。结论:UUO大鼠肾组织Wnt4/β-catenin信号通路活化,并可能介导了FGF-23的转录,而加味六味地黄汤可能通过阻断Wnt4/β-catenin信号通路的活化,下调FGF-23的表达,发挥抗肾间质纤维化作用。Objective:To observe the effect of Jiaweiliuweidihuang decoction on the protein expression of Wnt4,β-catenin,and Fibroblast growth factor-23(FGF-23)in the rat’s kidney with Unilateral ureteral obstruction(UUO).Methods:The 120 rats were divided into 4 groups randomly:sham group,Model group,Chinese medicine group and Valsartan group,there were 3 time points including 1 week,2 week,4 week.The rats both in the sham group and Model group were treated by intragastric administration of physiological saline(2 ml per day),and The rats in the Chinese medicine group were treated by intragastric administration of JiaWeiLiuWeiDiHuang decoction(2 ml per day).And The rats in the Valsartan group and were treated by intragastric administration of Valsartan(30 mg·kg^-1·d^-1).And the kidney pathology by HE and Masson stain,and the protein expression of Wnt4,β-catenin and FGF-23 in the kidney were detected by the way of Immunohistochemistry and Western blot.Results:The kidney structure in the sham group is regular.And the renal interstitial fibrosis in the Model group rats is found.However,the kidney pathology is improved in the Chinese medicine group.Our results indicated that,the level of Blood urea nitrogen and serum creatinine,the semi-quantitative scores,the protein expression of Wnt4,β-catenin and FGF-23 in the Model group are higher than those in the sham group.However,Both the Jiaweiliuweidihuang decoction and Valsartan treatment could reduce index including the level of Blood urea nitrogen and serum creatinine,the semi-quantitative scores,the protein expression of Wnt4,β-catenin and FGF-23.Conclusion:Jiaweiliuweidihuang decoction could provide an anti-Renal interstitial fibrosis role by blocking the activation of Wnt4/β-catenin pathway and suppressing the FGF-23 expression.

关 键 词：单侧输尿管梗阻 肾间质纤维化 加味六味地黄汤 Wnt4/β-catenin信号通路 纤维生长因子23 

分 类 号：R285.5[医药卫生—中药学]