摘要
目的 基于线粒体自噬探讨十味乳香散对痛风性肾炎大鼠的肾保护作用.方法 大鼠随机分为空白组,模型组,十味乳香散低、中、高剂量组(200、400、800 mg/kg),别嘌醇组(10 mg/kg),灌胃给予氧嗪酸钾(750 mg/kg)和尿酸(300 mg/kg)混悬液建立痛风性肾病大鼠模型.全自动生化分析仪、ELISA法和化学荧光法检测UA、SCr、BUN、SOD、XOD、MDA、ROS水平,HE染色观察肾组织病理变化,TUNEL 染色检测肾组织细胞凋亡情况,RT-qPCR法和Western blot 法检测 IL-1β、TNF-α、Bax、Bcl-2、caspase-3、caspase-9、PINK1、Parkin、LC3-Ⅱ mRNA和蛋白表达.结果 与模型组比较,十味乳香散各剂量组大鼠血清UA、BUN、SCr水平降低(P＜0.05),肾组织尿酸盐结晶沉积和肾组织细胞凋亡减少,肾组织ROS水平和炎性因子IL-1β、TNF-α水平降低(P＜0.05),肾组织线粒体自噬相关蛋白PINK1、Parkin、LC3-Ⅱ表达升高(P＜0.01).结论 十味乳香散可能通过降尿酸效应,抑制肾组织氧化应激、炎症反应,激活线粒体自噬通路等作用缓解大鼠痛风性肾损伤.
Abstract
AIM To investigate the renal protective effects of Shiwei Ruxiang Powder on gouty nephritis in rats based on mitophagy.METHODS Rats were randomly divided into the blank group,the model group,the low-dose,medium-dose,and high-dose Shiwei Ruxiang Powder groups(200,400,800 mg/kg)and allopurinol group(10 mg/kg).The rat model of gouty nephropathy was established by gavage of potassium oxyzinate(750 mg/kg)and uric acid(300 mg/kg).The rats had their levels of UA,SCr,BUN,XOD,SOD,MDA,ROS measured by automatic biochemical analyzer,ELISA and chemical fluorescence method;their renal pathological changes observed by HE staining;their apoptosis of renal tissue cells observed by TUNEL staining;and their mRNA and protein expressions of IL-1β,TNF-α,Bax,Bcl-2,caspase-3,caspase-9,PINK1,Parkin and LC3-Ⅱ detected by RT-qPCR and Western blot.RESULTS Compared with the model group,Shiwei Ruxiang Powder groups displayed dose-dependently decreased serum levels of UA,BUN and SCr,renal deposition of urate crystal and apoptosis(P<0.05);decreased renal levels of ROS and inflammatory factors IL-1β and TNF-α(P<0.05);and increased renal expressions of mitochondrial autophagy-related proteins PINK1,Parkin and LC3-Ⅱ(P<0.01).CONCLUSION Shiwei Ruxiang Powder may relieve gouty kidney injury in rats by reducing the uric acid level,the renal oxidative stress and inflammatory response,and activating mitophagy pathway as well.
基金项目
国家自然科学基金(81470247)
西藏自治区科技厅中央引导地方科技发展项目(XZ202202YD0020C)
维普
万方数据