摘要
目的:探讨六味地黄汤(LWDHD)对单侧输尿管梗阻(UUO)诱导的肾纤维化大鼠肾组织中整合素β1(Integrin-β1)、整合素连接激酶(ILK)及EMT相关因子锌指转录因子(Snail)、平滑肌肌动蛋白(α-SMA)、波形蛋白(Vimentin)和上皮钙黏蛋白(E-cadherin)表达的影响,研究其潜在抑制肾纤维化的作用。方法:选取48只SPF级雄性SD大鼠,复制UUO肾纤维化大鼠模型。随机分为假手术对照组、模型对照组、六味地黄汤3.38、6.75、13.5 g/kg组、依那普利10 mg/kg组。造模成功后,大鼠分别灌胃相应药物或生理盐水,持续2 w。于第2周末检测血清中的肌酐(Crea)、尿素氮(BUN)含量;采用HE染色和Masson染色观察肾组织变化及胶原纤维沉积情况;Western blot法、免疫组织化学染色法和RT-qPCR法分别检测肾组织Integrin-β1、ILK、Snail、α-SMA、Vimentin和E-cadherin的蛋白及mRNA表达。结果:与假手术对照组比较,模型对照组大鼠血清Crea和BUN含量明显升高(P<0.05),肾小管萎缩甚至消失,肾间质发生纤维化,同时见炎细胞浸润,胶原纤维沉积较为显著,肾组织中Integrin-β1、ILK、Snail、α-SMA、Vimentin蛋白表达和mRNA表达明显上调(P<0.05),E-cadherin蛋白表达和mRNA表达下调(P<0.05);与模型对照组比较,六味地黄汤各组大鼠血清Crea和BUN含量明显降低(P<0.05),肾脏病理状态和胶原纤维沉积不同程度改善,肾组织中Integrin-β1、ILK、Snail、α-SMA、Vimentin蛋白表达和mRNA表达均明显下调(P<0.05),E-cadherin蛋白表达和mRNA表达上调(P<0.05)。结论:六味地黄汤可以减轻UUO大鼠肾组织病理损伤,改善肾纤维化,其潜在作用机制可能与下调肾组织Integrin-β1/ILK/Snail信号通路表达,进而抑制肾小管上皮细胞转分化进程有关。
Objective:To investigate the effects of Liuwei Dihuang Decoction(六味地黄汤,LWDHD)on the expression of Integrin-β1,Integrin-linked kinase(ILK),and EMT-related markers,including the zinc finger transcription factor Snail,α-smooth muscle actin(α-SMA),Vimentin,and E-cadherin,in the renal tissue of rats with unilateral ureteral obstruction(UUO)-induced renal fibrosis,and to explore its potential role in suppressing renal fibrosis.Methods:Forty-eight SPF-grade male SD rats were used to establish the UUO renal fibrosis model.Rats were randomly assigned to six groups:sham operation,model control,LWDHD at doses of 3.38,6.75,and 13.5 g/kg,and enalapril 10 mg/kg.After successful modeling,rats were administered the corresponding treatments or saline by gavage for 2 weeks.At the end of the second week,serum creatinine(Crea)and blood urea nitrogen(BUN)levels were measured.HE and Masson staining were performed to observe renal pathological changes and collagen fiber deposition.Protein and mRNA expression levels of Integrin-β1,ILK,Snail,α-SMA,Vimentin,and E-cadherin in renal tissues were detected using Western blot,immunohistochemistry,and RT-qPCR.Results:Compared with the sham operation group,the model control group exhibited significantly increased Crea and BUN levels(P<0.05),renal tubular atrophy or disappearance,interstitial fibrosis,infiltration of chronic inflammatory cells,and marked collagen fiber deposition.Protein and mRNA expression levels of Integrin-β1,ILK,Snail,α-SMA,and Vimentin were significantly upregulated(P<0.05),whereas E-cadherin expression was downregulated(P<0.05).Compared with the model control group,all LWDHD treatment groups showed significantly reduced Crea and BUN levels(P<0.05),improved renal pathology,and decreased collagen fiber deposition.Furthermore,renal tissue expression levels of Integrin-β1,ILK,Snail,α-SMA,and Vimentin were significantly downregulated(P<0.05),while E-cadherin expression was upregulated(P<0.05).Conclusion:LWDHD can alleviate renal pathological damage and improve renal fibrosis in UUO rats.Its potential mechanisms may involve downregulation of the Integrin-β1/ILK/Snail signaling pathway,thereby inhibiting the transdifferentiation of renal tubular epithelial cells.
作者
孟斌
赵欣然
朱天煜
蒋志兵
谭夕雅
郭金晶
吴薇羽
唐群
MENG Bin;ZHAO Xinran;ZHU Tianyu;JIANG Zhibing;TAN Xiya;GUO Jinjing;WU Weiyu;TANG Qun(Medical College,Hunan University of Chinese Medicine,Changsha 410208)
出处
《中药药理与临床》
北大核心
2026年第3期2-9,共8页
Pharmacology and Clinics of Chinese Materia Medica
基金
湖南中医药大学校级科研项目(编号:Z2023XJYB04)
湖南省自然科学基金项目(编号:2025JJ90041)
湖南省研究生科研创新项目(编号:CX20251206)
湖南省教育厅科学研究项目(编号:25C0209)。
