益肾化湿颗粒通过miR-339-5p靶向调控TGF-β1/Smad通路对慢性肾小球肾炎模型大鼠的肾脏保护作用及其机制研究  

Study on the renal protective effect and mechanism of Yishen Huashi granules in chronic glomerulonephritis model rats by targeting and regulating TGF-β1/Smad pathway through miR-339-5p

作　　者：孙源博 张洋 李桂芹 李钰 于伟光 SUN Yuanbo;ZHANG Yang;LI Guiqin;LI Yu;YU Weiguang(Department of Nephrology,Hongqi Hospital Affiliated to Mudanjiang Medical College,Heilongjiang Mudanjiang 157000,China;Department of General Surgery,Hongqi Hospital Affiliated to Mudanjiang Medical College,Heilongjiang Mudanjiang 157000,China)

机构地区：[1]牡丹江医学院附属红旗医院,肾脏内科,黑龙江牡丹江157000 [2]牡丹江医学院附属红旗医院,普外一科,黑龙江牡丹江157000

出　　处：《中国医院药学杂志》2023年第17期1907-1913,共7页Chinese Journal of Hospital Pharmacy

基　　金：黑龙江省省属高等学校基本科研业务费科研项目(编号:2019-KYYWF-0980;2020-KYYWF-0773)。

摘　　要：目的:探讨益肾化湿颗粒通过miR-339-5p靶向调控转化生长因子-β1(TGF-β1)/Smad通路对慢性肾小球肾炎模型大鼠的肾脏保护作用及其机制。方法:将SD大鼠分为假手术组、模型组、益肾化湿颗粒组、贝那普利组、益肾化湿颗粒+antagomir阴性对照(NC)组、益肾化湿颗粒+miR-339-5p antagomir组、益肾化湿颗粒+SRI-011381组。全自动生化分析仪检测大鼠24 h尿蛋白、血肌酐(Scr)、血尿素氮(BUN)水平;ELISA法检测血清中肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-1β、IL-6水平;qRT-PCR检测肾组织中miR-339-5p表达;免疫组化检测大鼠肾组织中核因子E2相关因子2(NRF2)、血红素氧合酶1(HO-1)蛋白表达;HE、Masson染色分别检测大鼠肾组织病理变化、纤维化程度;Western blot检测肾组织中TGF-β1、p-Smad2/3、Smad7蛋白表达;验证miR-339-5p与TGF-β1的关系。结果:与假手术组比较,模型组大鼠肾功能异常,氧化应激增强,肾组织病理损伤及纤维化严重,炎性因子、TGF-β1、p-Smad2/3蛋白表达升高,miR-339-5p表达、Smad7蛋白表达降低(P<0.05);与模型组比较,益肾化湿颗粒组、贝那普利组对应指标变化趋势与上述相反(P<0.05);miR-339-5p antagomir或SRI-011381减弱了益肾化湿颗粒对慢性肾小球肾炎模型大鼠的肾脏保护作用。miR-339-5p靶向调控TGF-β1表达。结论:益肾化湿颗粒可能通过上调miR-339-5p靶向抑制TGF-β1/Smad通路对慢性肾小球肾炎模型大鼠肾脏发挥保护作用。OBJECTIVE To investigate the renal protective effect and mechanism of Yishen Huashi granules in chronic glomerulonephritis model rats by targeting and regulating transforming growth factor-β1(TGF-β1)/Smad pathway through miR-339-5p.METHODS SD rats were divided into sham operation group,model group,Yishen Huashi granules group,benazepril group,Yishen Huashi granules+antagomir negative control(NC)group,Yishen Huashi granules+miR-339-5p antagomir group,and Yishen Huashi granules+SRI-011381 group.The levels of 24 h urinary protein,serum creatinine(Scr)and blood urea nitrogen(BUN)of rats were measured by an automatic biochemical analyzer;the levels of serum tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and interleukin-6(IL-6)were detected by ELISA;the expression of miR-339-5p in renal tissue was detected by qRT-PCR;the expression of nuclear factor E2 related factor 2(NRF2)and heme oxygenase 1(HO-1)in rat kidney was detected by immunohistochemistry;HE and Masson staining were used to detect the pathological changes and the degree of fibrosis of rat kidney;Western blot was used to detect the expression of TGF-β1 p-Smad2/3 and Smad7 proteins in renal tissue;the relationship between miR-339-5p and TGF-β1 was verified.RESULTS Compared with the sham operation group,the model group had abnormal renal function,increased oxidative stress,severe renal tissue pathological damage and fibrosis,inflammatory factors,TGF-β1 and p-Smad2/3 protein expression increased,the expression of miR-339-5p and Smad7 proteins decreased(P<0.05);compared with that in the model group,the change trend of corresponding indexes in Yishen Huashi granules group and benazepril group was opposite to the above(P<0.05);miR-339-5p antagomir or SRI-011381 attenuated the renal protective effect of Yishen Huashi granules in chronic glomerulonephritis model rats.MiR-339-5p targeted and regulated the expression of TGF-β1.CONCLUSION Yishen Huashi granules may protect kidney of model rats with chronic glomerulonephritis by up-regulating miR-339-5p an

关 键 词：益肾化湿颗粒 转化生长因子-β1/Smad通路 慢性肾小球肾炎 炎症 

分 类 号：R966[医药卫生—药理学]