Wnt/β-catenin通路介导柴胡皂苷D治疗IgA肾病的疗效及作用机制研究  

Curative Effect and Mechanism of Saikosaponin D in IgA Nephropathy by Wnt/β-catenin Pathways

作　　者：王珍[1] 李仪[1] 李聪[1] WANG Zhen;LI Yi;LI Cong(The Tenth Affiliated Hospital of Southern Medical University(Dongguan People′s Hospital),Dongguan 523000,Guangdong,China)

机构地区：[1]南方医科大学附属东莞医院(东莞市人民医院),广东东莞523000

出　　处：《辽宁中医杂志》2023年第12期213-216,I0018,共5页Liaoning Journal of Traditional Chinese Medicine

基　　金：广东省中医药管理局项目(2009259);东莞市社会科技发展(重点)项目(202050715001208)。

摘　　要：目的观察柴胡皂苷D治疗IgA肾病模型大鼠的疗效,基于Wnt/β环形蛋白(β-catenin)信号通路探究其作用机制。方法将60只SD大鼠随机分为对照组、模型组(牛血清白蛋白+四氯化碳+脂多糖)、阳性对照组(贝那普利,10 mg/kg)、柴胡皂苷D组(1.5 mg/kg)和柴胡皂苷D+Wnt/β-catenin通路激活剂组(氯化锂,60 mg/kg)。连续给药8周后,测定24 h尿蛋白含量和血清肌酐、尿素氮含量,采用HE染色观察肾组织病理变化,Masson染色观察肾纤维化程度,RT-PCR、Western Blot法检测α平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)、钙黏附蛋白E(E-cadherin)、波形蛋白(Vimentin)、Wnt-1、β-catenin及糖原合成酶激酶-3β(glycogen synthase kinase-3β,GSK-3β)表达。结果与模型组比较,阳性对照组和柴胡皂苷D组24 h尿蛋白含量、肌酐、尿素氮含量、肾组织纤维化程度评分、α-SMA、Vimentin、Wnt-1、β-catenin mRNA及蛋白表达、GSK-3β磷酸化水平明显降低,E-cadherin mRNA及蛋白表达明显升高(P<0.05);添加Wnt/β-catenin通路激活剂氯化锂后,可逆转柴胡皂苷D对模型大鼠生理指标的改善作用。结论柴胡皂苷D可能通过抑制Wnt/β-catenin通路,改善IgA肾病模型大鼠的肾组织损伤,减轻肾纤维化程度。Objective To observe the curative effect of saikosaponin D on rats with IgA nephropathy and explore its action mechanism based on Wnt/β-catenin signaling pathways.Methods A total of 60 SD rats were randomly divided into control group,model group(bovine serum albumin+carbon tetrachloride+ipopolysaccharide),positive control group(benazepril,10 mg/kg),saikosaponin D group(1.5 mg/kg)and saikosaponin D+Wnt/β-catenin pathway activator group(lithium chloride,60 mg/kg).After 8 weeks of continuous administration,the levels of 24 h urinary protein,serum creatinine and blood urea nitrogen were detected.The pathological changes of renal tissues were observed by HE staining.The severity of renal fibrosis was observed by Masson staining,and expressions ofα-smooth muscle actin(α-SMA),E-cadherin,Vimentin,Wnt-1,β-catenin and glycogen synthase kinase-3β(GSK-3β)were detected by RT-PCR and Western Blot.Results Compared with those of the model group,the levels of 24 h urinary protein,creatinine and blood urea nitrogen,the score of renal fibrosis,expressions ofα-SMA,Vimentin,Wnt-1,β-catenin mRNA and proteins,and phosphorylation level of GSK-3βwere significantly decreased in positive control group and saikosaponin D group,while the expressions of E-cadherin mRNA and protein were significantly increased(P<0.05).The lithium chloride,an activator of Wnt/β-catenin pathways,could reverse the improvement effect of saikosaponin D on physiological indexes in model rats.Conclusion Saikosaponin D may relieve renal tissue injury and renal fibrosis in rats with IgA nephropathy by inhibiting Wnt/β-catenin pathways.

关 键 词：IGA肾病 柴胡皂苷D 肾纤维化 Wnt/β环形蛋白信号通路 

分 类 号：R285.5[医药卫生—中药学]