肾衰泄浊汤延缓腺嘌呤大鼠肾间质纤维化的机制研究  

Mechanism of Shenshuaixiezhuo Decoction delaying renal interstitial fibrosis in adenine rats

作　　者：陈微 李怀玉 陈思洁 吴国庆[2] 范伟[2] 肖亮[2] 杨军平[2] CHEN Wei;LI Huai-yu;CHEN Si-jie;WU Guo-qing;FAN Wei;XIAO Liang;YANG Jun-ping(Graduate School of Jiangxi University of Chinese Medicine,Nanchang 330004,China;Affiliated Hospital of Jiangxi University of Chinese Medicine,Nanchang 330006,China)

机构地区：[1]江西中医药大学研究生院,南昌330004 [2]江西中医药大学附属医院,南昌330006

出　　处：《时珍国医国药》2023年第7期1582-1586,共5页Lishizhen Medicine and Materia Medica Research

基　　金：国家自然科学基金(81260578);江西中医药大学校级研究生创新专项资金项目(JZYC21S08)。

摘　　要：目的观察肾衰泄浊汤对腺嘌呤致大鼠肾间质纤维化模型的影响,并基于TGF-β1介导的下游信号通路探讨其延缓肾间质纤维化可能存在的机制。方法将SD大鼠其分为正常组、模型组、肾衰泄浊汤组和氯沙坦组。除正常组外,其余三组采用21天腺嘌呤灌胃法进行慢性肾衰竭(CRF)造模。造模结束后,正常组和模型组给予生理盐水,中药组给予18.75g·kg^(-1)浓度的肾衰泄浊汤,西药组给予1.8 mg·kg^(-1)浓度的氯沙坦,每日1次,连续灌胃28d。取材后,采用HE染色和Masson染色观察肾组织病理组织变化;检测血肌酐(Scr)、尿素氮(BUN)的含量;酶联免疫法检测尿中胱抑素C(Cys-C)和血清中结缔组织生长因子(CTGF)、骨形态蛋白-7(BMP-7)的含量;qRT-PCR法和Western Blot法检测TGF-β1、Smad7、CTGF和BMP-7的mRNA和蛋白的表达;免疫组化法检测α-平滑肌肌动蛋白(α-SMA)、Ⅰ型胶原蛋白(collagenⅠ)和纤连蛋白(FN)的表达情况。结果与模型组相比,肾衰泄浊汤可以降低CRF大鼠血清Scr、BUN、CTGF的含量(P<0.01),提高血清BMP-7的含量(P<0.05),降低尿液Cys-C的含量(P<0.05);改善炎性细胞浸润及纤维化等病理情况;降低肾组织TGF-β1、CTGF的mRNA和蛋白表达(P<0.05),提高Smad7、BMP-7的mRNA和蛋白表达(P<0.05);降低肾组织α-SMA、CollagenⅠ、FN的阳性表达水平(P<0.01)。结论肾衰泄浊汤能够改善CRF大鼠肾间质纤维化情况,其机制可能是通过干预TGF-β1/Smad信号通路,抑制或缓解细胞外基质(ECM)堆积。Objective To observe the effect of Shenshuaixiezhuo Decoction on adenine-induced renal interstitial fibrosis in rats,and to explore the possible mechanism of its delay of renal interstitial fibrosis based on TGF-β1 mediated downstream signaling pathway.Methods SD rats were divided into normal group,model group,Shenshuaixiezhuo Decoction group and losartan group.In addition to normal group,the other three groups were given 21 days adenine instillation to establish chronic renal failure(CRF)model.After modeling,the normal group and model group were given normal saline,the traditional Chinese medicine group was given Shenshuaixiezhuo Decoction(18.75g·kg^(-1)),and the western medicine group was given losartan(1.8 mg·kg^(-1)),once a day,by gavage for 28 days.After sampling,HE staining and Masson staining were used to observe the pathological changes of renal tissues.Serum creatinine(Scr),urea nitrogen(BUN)content;Cystatin C(Cys-C)in urine and connective tissue growth factor(CTGF)and bone morphoprotein-7(BMP-7)in serum were detected by enzyme-linked immunosorbent assay.The mRNA and protein expressions of TGF-β1,Smad7,CTGF and BMP-7 were detected by qRT-PCR and Western Blot.The expressions ofα-smooth muscle actin(α-SMA),CollagenⅠand fibronectin(FN)were detected by immunohistochemistry.Results Compared with the model group,Shenshuaixiezhuo Decoction could reduce the contents of Scr,BUN and CTGF in serum(P<0.01),increase the content of BMP-7 in serum(P<0.05),and decrease the content of Cys-C in urine(P<0.05).Improve inflammatory cell infiltration and fibrosis and other pathological conditions;The mRNA and protein expressions of TGF-β1 and CTGF were decreased(P<0.05),while the mRNA and protein expressions of Smad7 and BMP-7 were increased(P<0.05).The positive expression levels ofα-SMA,collagenⅠand FN in renal tissue were decreased(P<0.01).Conclusion Shenshuaixiezhuo Decoction can improve renal interstitial fibrosis in CRF rats,possibly by interfering TGF-β1/Smad signaling pathway and inhibiting or alleviating

关 键 词：慢性肾衰竭 肾间质纤维化 肾衰泄浊汤 TGF-Β1/SMAD信号通路 ECM 

分 类 号：R285.5[医药卫生—中药学]