摘要
目的基于TGF-β1/Smad通路和基质金属蛋白酶水平探讨复方丹参片对肾纤维化大鼠的保护作用及相关机制。方法采用灌胃腺嘌呤(250 mg·kg^(-1))的方式制备肾纤维化大鼠模型。将大鼠随机分为正常组、模型组、氯沙坦组(0.09 g·kg^(-1))及复方丹参低(0.3 g·kg^(-1))、高(0.6 g·kg^(-1))剂量组。各组大鼠给予相应剂量灌胃给药,每日1次,连续干预4周。检测大鼠血清Cr、BUN水平;采用HE及Masson染色法观察肾脏组织病理形态及纤维化程度;采用免疫组织化学法检测肾脏组织中TGF-β1、Smad2、Smad3、Smad7蛋白表达水平;采用Western Blot法检测肾脏组织中MMP-2、MMP-9、TIMP-1蛋白表达水平。结果与正常组比较,模型组大鼠血清Cr、BUN水平明显升高(P<0.05);肾脏出现明显纤维化病变;肾脏组织中TGF-β1、Smad2、Smad3、TIMP-1蛋白表达水平明显升高(P<0.05),Smad7、MMP-2、MMP-9蛋白表达水平明显降低(P<0.05)。与模型组比较,低、高剂量复方丹参片均能明显降低大鼠血清Cr、BUN水平(P<0.05);明显改善肾脏纤维化病变;降低肾脏组织中TGF-β1、Smad2、Smad3、TIMP-1蛋白表达水平(P<0.05),升高Smad7、MMP-2、MMP-9蛋白表达水平(P<0.05)。结论复方丹参片可能通过抑制TGF-β1/Smad通路及提高基质金属蛋白酶水平来实现对肾纤维化大鼠的保护作用。
Objective To investigate the protective effect and related mechanisms of compound Danshen Tablets on renal fibrosis rats based on TGF-β1/Smad pathway and matrix metalloproteinase levels.Methods The rat model of renal fibrosis was prepared by gavage of adenine(250 mg·kg^(-1)). The rats were randomly divided into normal group,model group,losartan group(0.09 g·kg^(-1))and compound Danshen low-dose(0.3 g·kg^(-1))and high-dose(0.6 g·kg^(-1))groups. Rats in each group were given corresponding dose of intragastric administration every day for 4 continuous weeks. The levels of serum Cr and BUN were detected;HE and Masson staining were used to observe the pathological morphology and fibrosis degree of kidney;Immunohistochemistry was used to detect the protein expression levels of TGF-β1, Smad2, Smad3 and Smad7 in renal tissues. Western Blot was used to detect the protein expression levels of MMP-2,MMP-9 and TIMP-1 in kidney tissues.Results Compared with normal group,the levels of serum Cr and BUN in model group were significantly increased(P<0.05);The kidney showed obvious fibrosis;The protein expression levels of TGF-β1,Smad2,Smad3 and TIMP-1 were significantly increased(P<0.05),while the protein expression levels of Smad7,MMP-2 and MMP-9 were significantly decreased(P<0.05).Compared with model group,low-and high-dose of compound Danshen Tablets could significantly reduce the levels of serum Cr and BUN in rats(P<0.05);the renal fibrosis was significantly improved;the protein expression levels of TGF-β1,Smad2,Smad3 and TIMP-1 in renal tissue decreased(P<0.05),and the protein expression levels of Smad7, MMP-2 and MMP-9 in renal tissue increased(P<0.05).Conclusion Compound Danshen Tablets may achieve protective effects in rats with renal fibrosis by inhibiting the TGF-β1/Smad pathway and increasing matrix metalloproteinase levels.
作者
张明昊
高一盈
赵盈盈
赵丹萍
徐一凡
于凌爽
姚文佳
刘丹丹
王灿
ZHANG Minghao;GAO Yiying;ZHAO Yingying;ZHAO Danping;XU Yifan;YU Lingshuang;YAO Wenjia;LIU Dandan;WANG Can(l.School of Medicine,Henan University of Chinese Medicine,Zhengzhou 450046 Henan,China;School of Pharmacy,Henan University of Chinese Medicine,Zhengzhou 450046 Henan,China;School of Rehabilitation Medicine,Henan University of Chinese Medicine,Zhengzhou 450046 Henan,China)
出处
《中药新药与临床药理》
CAS
CSCD
北大核心
2022年第3期300-306,共7页
Traditional Chinese Drug Research and Clinical Pharmacology
基金
国家自然科学基金项目(31372270)
河南中医药大学科研苗圃工程项目(MP2020-01)。
作者简介
张明昊,男,高级实验师,研究方向:中药药理学。Email:zhangminghao@hactem.edu.cn。;通信作者:王灿,女,副教授,研究方向:中药药理学。Email:wangjiucan@163.com。
