摘要
目的评估肾衰泄浊汤对腺嘌呤灌胃所致慢性肾衰(Chronic renal failure,CRF)大鼠的改善作用,并从转化生长因子-β1(Transforming growth factor beta1,TGF-β1)/Smads通路探究其抗肾间质纤维化(Renal interstitial fibrosis,RIF)的机制。方法将60只SD大鼠随机分为6组:正常组、模型组、中药9.375 g·kg^(-1)、18.75 g·kg^(-1)、37.5 g·kg^(-1)组和氯沙坦钾组,每组10只,除正常组外,其余各组腺嘌呤灌胃复制CRF大鼠模型。给药阶段,正常组与模型组给予生理盐水,中药9.375 g·kg^(-1)、18.75 g·kg^(-1)和37.5 g·kg^(-1)组分别灌胃相应浓度的肾衰泄浊汤,阳性对照给予1.8 mg·kg^(-1)浓度的氯沙坦钾,每天1次,连续28天。检测血清中的血肌酐(Serum creatinine,Scr)、尿素氮(Blood urea nitrogen,BUN)和β2微球蛋白(β2 microglobulin,β2-MG)含量;HE染色观察肾组织的病理变化;ELISA法测定血清中的TGF-β1含量;RT-PCR法和Western blot法检测肾组织Smad3、Smad4的mRNA和蛋白表达。结果与模型组相比,肾衰泄浊汤能降低CRF大鼠血清Scr(9.375 g·kg^(-1)、18.75 g·kg^(-1)和37.5 g·kg^(-1):P<0.01)、BUN(18.75 g·kg^(-1)与37.5 g·kg^(-1):P<0.01)及β2-MG(18.75 g·kg^(-1)与37.5 g·kg^(-1):P<0.01)的含量;减轻肾组织的病理损害;降低血清中TGF-β1(18.75 g·kg^(-1)与37.5 g·kg^(-1):P<0.01)的水平;下调肾组织中Smad3与Smad4的mRNA(Smad3:9.375g·kg^(-1)、18.75g·kg^(-1)和37.5g·kg^(-1):P<0.01;Smad4:18.75 g·kg^(-1):P<0.05,37.5 g·kg^(-1):P<0.01)与蛋白(Smad3与Smad4:18.75 g·kg^(-1)与37.5 g·kg^(-1):P<0.01)表达水平。结论肾衰泄浊汤能减轻腺嘌呤灌胃所致CRF大鼠的肾脏损伤,其抗RIF机制可能与抑制TGF-β1/Smads信号通路有关,具体作用机制待后续研究以进一步深入。
Objective To evaluate the ameliorating effect of Shenshuaixiezhuo Decoction on chronic renal failure(CRF)induced by adenine ingastric administration in rats,and to explore its potential mechanism of anti-renal interstitial fibrosis(RIF)from the transforming growth factor beta1(TGF-β1)/Smads pathway.Methods 60 SD rats were randomly divided into 6 groups:normal group,model group,Chinese medicine 9.375 g·kg^(-1),18.75 g·kg^(-1),37.5 g·kg^(-1) group and losartan potassium group with 10 rats in each group.During administration stage,normal group and model group were given normal saline;Chinese medicine 9.375 g·kg^(-1),18.75 g·kg^(-1) and 37.5 g·kg^(-1) groups were given corresponding concentrations of Shenshuaixiezhuo Decoction respectively;medicine groups was given 1.8 mg·kg^(-1) kosuya,once a day,for consecutive 28 day.The contents of serum creatinine(Scr),blood urea nitrogen(BUN)andβ2 microglobulin(β2-MG)in serum were detected.The pathological changes of renal tissue after HE staining were observed.The content of TGF-β1 in serum was determined by ELISA.The mRNA expressions of Smad3 and Smad4 protein in renal tissues were detected by RT-PCR and Western blot.Results Compared with model group,Shenshuaixiezhuo Decoction could improve the contents of Scr(9.375 g·kg^(-1),18.75 g·kg^(-1) and 37.5 g·kg^(-1):P<0.01),BUN(18.75 g·kg^(-1) and 37.5 g·kg^(-1):P<0.01)andβ2-Mg(18.75 g·kg^(-1) and 37.5 g·kg^(-1):P<0.01)in serum of CRF rats;reduce the pathological damage of renal tissue;decrease the level of TGF-β1 in serum(18.75 g·kg^(-1) and 37.5 g·kg^(-1):P<0.01).The mRNA levels of Smad3 and Smad4 in renal tissues were down-regulated(Smad3:9.375 g·kg^(-1),18.75 g·kg^(-1) and 37.5 g·kg^(-1):P<0.01;Smad4:18.75 g·kg^(-1):P<0.05,37.5 g·kg^(-1):P<0.01)and protein(Smad3,Smad4:18.75 g·kg^(-1) and 37.5 g·kg^(-1):P<0.01).Conclusion Shenshuaixiezhuo Decoction can alleviate renal damage induced by adenine ingastric administration in CRF rats,and its anti-fibrosis mechanism may be related to the inhibition of TGF-β1/Smads signaling pathway,and the specific mechanism needs further study.
作者
李怀玉
邱丽瑛
陈微
李玮婷
付勇
简钰乘
杨军平
Li Huaiyu;Qiu Liying;Chen Wei;Li Weiting;Fu Yong;Jian Yucheng;Yang Junping(Graduate School,Jiangxi University of Chinese Medicine,Nanchang 330004,China;Affiliated Hospital of Jiangxi University of Chinese Medicine,Nanchang 330006,China)
出处
《世界科学技术-中医药现代化》
CSCD
北大核心
2023年第5期1743-1749,共7页
Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology
基金
国家自然科学基金委员会地区科学基金项目(81260578):基于GRC的慢性肾衰大鼠微血管保护与泻浊延缓机制研究,负责人:杨军平
江西中医药大学校级科技创新团队发展计划(CXTD22012):力敏腧穴科技创新团队,负责人:付勇
