湖南中医药大学学报2025，Vol.45Issue(4)：608-616,9.DOI:10.3969/j.issn.1674-070X.2025.04.004
基于TGF-β1/Smad信号通路探讨天芙止眩方改善自发性高血压大鼠肾纤维化的作用机制
Mechanism of Tianfu Zhixuan Formula in alleviating renal fibrosis in spontaneously hypertensive rats based on the TGF-β1/Smad signaling pathway
摘要
Abstract
Objective To explore the alleviative effects of Tianfu Zhixuan Formula(TFZXF)on renal fibrosis and inflammation in spontaneously hypertensive rats(SHR)based on the transforming growt h factor-β1(TGF-β1)/Smad signaling pathway.Methods Forty SHR rats were randomly divided into five groups:a model group,an irbesartan group(13.5 mg/kg),and high-(5.94 g/kg),medium-(2.97 g/kg),and low-(1.49 g/kg)dose TFZXF groups,with eight rats in each group.Another eight WKY rats were used as the normal group.The model groups and the normal group were given an equal volume of distilled water.All groups were administered by gavage for 11 consecutive weeks,once a day.The systolic and diastolic blood pressures of the rats'tail artery were measured at weeks 1,3,5,7,9,and 11.After the experiment,the levels of blood urea nitrogen(BUN)and creatinine(Scr)in the serum were measured by the biochemical analyzer.The levels of angiotensinⅡ(AngⅡ),interleukin-1β(IL-1β),and tumor necrosis factor-α(TNF-α)in the serum were measured by ELISA.The pathological changes and collagen fiber deposition in renal tissue were measured by HE,Masson,and Sirius red staining.The expressions of typeⅠ collagen(CollagenⅠ),typeⅢ collagen(CollagenⅢ),TGF-β1,and CD68 proteins in renal tissue were measured by immunohistochemical staining.The protein expressions of CD68 and TGF-β1 in renal tissue,as well as the protein ratios of phosphorylated cellular signal transduction molecules Smad2/3(p-Smad2/3)to cellular signal transduction molecules 2/3(Smad2/3),were measured by Western blot.And the mRNA expressions of AngⅡ,TGF-β1,and CD68 were measured by RT-qPCR.Results Compared with the control group,the SHR rats in the model group showed increased systolic and diastolic blood pressure at weeks 1,3,5,7,9,and 11(P<0.001).The levels of serum BUN,Scr,AngⅡ,IL-1β,and TNF-α were higher(P<0.01,P<0.001).The renal tissue in the model group exhibited pathological damage,inflammatory infiltration,and significant fibrosis.The protein expressions of CollagenⅠ and CollagenⅢ increased(P<0.001).The protein expression levels of CD68 and TGF-β1,the protein ratio of p-Smad2/3 and Smad2/3,as well as the mRNA levels of AngⅡ,TGF-β1,and CD68,were all higher(P<0.01,P<0.001).Compared with the model group,the irbesartan group and the high-and medium-dose TFZXF groups showed decreased systolic and diastolic blood pressure at weeks 3,5,7,9,and 11(P<0.01).The low-dose TFZXF group showed decreased systolic and diastolic blood pressure at weeks 5,7,9,and 11(P<0.05,P<0.01).The levels of serum BUN,Scr,AngⅡ,IL-1β,and TNF-α decreased(P<0.05,P<0.01).The pathological damage in the renal tissue was significantly relieved,with reduced inflammatory infiltration and fibrosis.The protein expressions of CollagenⅠ and CollagenⅢdecreased(P<0.05,P<0.01).The protein expression levels of CD68 and TGF-β1,the protein ratio of p-Smad2/3 and Smad2/3,as well as the mRNA levels of AngⅡ,TGF-β1,and CD68,were all lower(P<0.05,P<0.01).Conclusion Treatment with TFZXF can effectively reduce blood pressure and alleviate hypertension-induced renal fibrosis in SHR rats.The mechanism may be related to reducing tissue inflammation and inhibiting the TGF-β1/Smad signaling pathway.关键词
高血压/天芙止眩方/肾纤维化/巨噬细胞/TGF-β1/Smad信号通路Key words
hypertension/Tianfu Zhixuan Formula/renal fibrosis/macrophages/TGF-β1/Smad signaling pathway分类
中医学引用本文复制引用
江丽红,姚强,罗晨,陆华冠,王宇红,刘建军..基于TGF-β1/Smad信号通路探讨天芙止眩方改善自发性高血压大鼠肾纤维化的作用机制[J].湖南中医药大学学报,2025,45(4):608-616,9.基金项目
湖南省自然科学基金项目(2024JJ8158) （2024JJ8158）
湖南中医药大学科研创新基金项目(2023BKS146) （2023BKS146）
湖南中医药大学研究生创新课题(2024CX078). （2024CX078）
