摘要
目的探讨金雀异黄酮对自发性高血压大鼠(SHR)肾纤维化及转化生长因子-β1(TGF-β1)/Smads信号通路的影响。方法取40只清洁级雄性12周龄SHR按随机数字表法分为模型组、依那普利(10 mg/kg)组和金雀异黄酮低(7.5 mg/kg)、中(15 mg/kg)、高(30 mg/kg)剂量组,每组8只;另取8只清洁级雄性12周龄Wistar-Kyoto(WKY)大鼠设为正常对照组。1次/d灌胃给药治疗6周,测量收缩压(SBP)和舒张压(DBP),检测血清尿酸(UA)、肌酐(SCr)、尿素氮(BUN)、血管紧张素Ⅱ(AngⅡ)水平;称量肾脏质量并计算肾脏指数(肾脏质量/体质量);通过HE染色观察肾组织病理学改变,Masson染色观察肾组织纤维化状况;Western blot检测肾组织TGF-β1、Smad2、p-Smad2、Smad3、p-Smad3、Smad7、胶原蛋白(Col)-Ⅰ、Col-Ⅲ蛋白表达。结果与模型组相比,依那普利组和金雀异黄酮中、高剂量组大鼠SBP、DBP、UA、SCr、BUN、AngⅡ、肾脏质量、肾脏指数均明显降低(P<0.05);肾组织病理学改变及肾组织纤维化状况均明显改善,胶原容积分数(CVF)明显降低(P<0.05);TGF-β1、Col-Ⅰ、Col-Ⅲ蛋白表达量及p-Smad2/Smad2、p-Smad3/Smad3比值明显降低,Smad-7蛋白表达量明显升高(P<0.05)。金雀异黄酮低、中、高剂量组对除肾脏质量外其它指标的作用呈现剂量依赖性,并且金雀异黄酮高剂量组对除SBP、DBP、BUN、Col-I外其它指标的作用明显优于依那普利组(P<0.05)。结论金雀异黄酮具有降低SHR血压、改善肾纤维化的作用,其机制可能与调节TGF-β1/Smads信号通路有关。
Objective To investigate the effects of Genistein on renal fibrosis and transforming growth factor-β1(TGF-β1)/Smads signaling pathway in spontaneously hypertensive rats(SHR).Methods According to random number table method,40 male SHR were divided into model group,Enalapril(10 mg/kg)group and Genistein low(7.5 mg/kg),medium(15 mg/kg),high dose(30 mg/kg)group,with 8 rats in each group.And another 8 Wistar-Kyoto(WKY)rats were set as normal control group.6 weeks after treatment by gavage once a day,the systolic blood pressure(SBP)and diastolic blood pressure(DBP)were measured,the levels of serum uric acid(UA),creatinine(SCr),urea nitrogen(BUN)and angiotensinⅡ(AngⅡ)were detected.The renal mass was weighted and the renal index(renal mass/body mass)was calculated.The renal histopathology was observed by HE staining and renal fibrosis was observed by Masson staining.The expressions of TGF-β1,Smad2,p-Smad2,Smad3,p-Smad3,Smad7,collagen(Col)-I and Col-Ⅲin renal tissues were detected by Western blotting.Results Compared with the normal group,the SBP,DBP,UA,SCr,BUN,AngⅡ,renal mass,renal index of Enalapril group and Genistein medium,high dose group were significantly decreased(P<0.05).The renal histopathological changes and renal fibrosis were significantly improved,and the collagen volume fraction(CVF)was significantly reduced(P<0.05).The expression of TGF-β1,Col-Ⅰ,Col-Ⅲand the ratio of p-Smad2/Smad2,p-Smad3/Smad3 in renal tissue were significantly decreased,while the expression of Smad7 was significantly increased(P<0.05).Except for renal mass,the effects of Genistein low,medium,high dose groups on other indexes were dose-dependent.Except for SBP,DBP,BUN and Col-I,the effects of Genistein high dose group on other indexes were significantly better than those of enalapril group(P<0.05).Conclusion Genistein can reduce blood pressure and improve renal fibrosis of SHRs,which mechanism may be related to the regulation of TGF-β1/Smads signaling pathway.
作者
陈洁
杨林燕
苗盈盈
孙楠
郝海英
朱敏杰
袁铮
CHEN Jie;YANG Linyan;MIAO Yingying;SUN Nan;HAO Haiying;ZHU Minjie;YUAN Zheng(The Second Department of Nephrology,Handan Central Hospital,Handan 056000,Hebei,China)
出处
《西部医学》
2025年第7期974-980,共7页
Medical Journal of West China
基金
河北省医学科学研究课题计划(20211577)。
