摘要
目的:观察补肾开玄方对糖尿病肾病(DKD)大鼠肾纤维化的作用并探讨其机制。方法:采用高糖高脂饮食喂养联合腹腔注射链脲佐菌素(STZ)的方法建立DKD大鼠模型。将大鼠随机分为正常组、模型组、补肾开玄方低、中、高剂量组(分别给予补肾开玄方4、8、16 g·kg^(-1)·d^(-1))、二甲双胍组(二甲双胍,300 mg·kg^(-1)·d^(-1)),每组6只。每周定期测量大鼠体质量及血糖状况,实验结束时检测各组大鼠血清胰岛素(INS)、血肌酐(Scr)、尿素氮(BUN)、血尿酸(UA)含量;ELISA法检测血清过氧化氢酶(CAT)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、丙二醛(MDA)、一氧化氮(NO)及相关炎症因子肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)水平;HE染色观察肾组织病理改变;免疫组化法对大鼠肾脏中纤连蛋白(FN)、E-钙黏蛋白(E-cad)进行染色并分析;Western blot法检测肾脏TGF-β1/Smad通路相关因子TGF-β1、Smad3、Smad7的蛋白表达水平。结果:与模型组相比,补肾开玄方各剂量组与二甲双胍组的BUN、Scr、UA、MDA、NO、IL-6、TNF-α、Smad7水平降低,INS、SOD、GSH-Px、E-cad、TGF-β1、Smad3水平升高,差异具有统计学意义(P<0.05);经HE染色后,各治疗组较模型组肾组织病理损伤有明显改善。与二甲双胍组相比,补肾开玄方中、高剂量组可明显降低DKD大鼠BUN、Scr、MDA、NO、IL-1β、IL-6、TNF-α水平,升高INS、CAT、SOD、GSH-Px水平,差异具有统计学意义(P<0.05),且补肾开玄方中剂量组可降低UA、MDA、Smad7水平,升高Smad3水平,差异具有统计学意义(P<0.05)。结论:补肾开玄方可明显减轻糖尿病肾病大鼠肾纤维化,改善肾功能,其机制与缓解氧化应激损伤、减轻炎症反应、抑制细胞外基质堆积、减少系膜间质转化、调控TGF-β1/Smad信号通路有关。
Objective:To observe the effect of Bushen Kaixuan Formula(BKF)on renal fibrosis in rats with diabetic kidney disease(DKD)and explore its mechanism.Methods:The DKD rat model was established by the method of high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin(STZ).The rats were randomly divided into blank group,model group,BKF low,medium and high dose groups(4,8,16 g/kg·d),and metformin group(metformin,300 mg/kg·d),with 6 rats in each group.Body mass and blood glucose were measured weekly.At the end of the experiment,the serum insulin(INS),blood creatinine(SCr),urea nitrogen(BUN),and blood uric acid(UA)in each group were detected;serum catalase(CAT),superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),malondialdehyde(MDA),nitric oxide(NO)and related inflammatory factors were detected by ELISA.Examples of related inflammatory factors include tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and interleukin-6(IL-6).Western blot method was used for detecting the protein expression levels of renal TGF-β1/Smad pathway related factor TGF-β1,Smad3 and Smad7.Results:Compared with the model group,levels of BUN,Scr,UA,MDA,NO,IL-6,TNF-αand Smad7 were decreased in each dose groups of Bushen Kaixuan Formula and the metformin group,while levels of INS,SOD,GSH-Px,E-cadherin(E-cad),TGF-β1 and Smad3 were increased,the difference was statistically significant(P<0.05).After HE staining,the pathological injury of kidney tissue in all treatment groups showed significant improvement compared to that in the model group.In comparison with the metformin group,the dose of mediumgroup andthe dose of high group of Bushen Kaixuan Formula,the levels of BUN,Scr,MDA,NO,IL-1β,IL-6 and TNF-αwere significantly decreased,while the levels of INS,CAT,SOD and GSH-Px wereincreased,the difference was statistically significant(P<0.05).In addition,the levels of UA,MDA,Smad7 decreased,and the levels of Smad3 increased in the dose of medium group,the difference was statistically significant(P<0.05).Conclus
作者
马晶晶
朱翠翠
黄风玲
尚智涛
张社峰
杨辰华
MA Jingjing;ZHU Cuicui;HUANG Fengling;SHANG Zhitao;ZHANG Shefeng;YANG Chenhua(Zhoukou City Hospital of Traditional Chinese Medicine,Zhoukou 466000,China;Affiliated Hospital of Henan Provincial Institute of Traditional Chinese Medicine,Zhengzhou 450004,China;Henan University of Chinese Medicine,Zhengzhou 450046,China)
出处
《中医药学报》
CAS
2024年第12期32-37,共6页
Acta Chinese Medicine and Pharmacology
基金
河南省中医药科学研究专项课题(20-21ZY1066)
