芪术颗粒对单侧输尿管梗阻小鼠肾组织PI3K/AKT/GSK3β/MAPK信号通路的影响  

Effects of Qizhu Granules on PI3K/AKT/GSK3β/MAPK signaling pathway in unilateral ureteral obstruction mouse’s renal tissue

作　　者：彭菊琴 王攀 侯敏 高文静 陈潇潇 杜阳 于清源 任钧国[1] PENG Ju-qin;WANG Pan;HOU Min;GAO Wen-jing;CHEN Xiao-xiao;DU Yang;YU Qing-yuan;REN Jun-guo(Institute of Basic Medicine,Xiyuan Hospital,China Academy of Chinese Medical Sciences/Beijing Key Laboratory of Traditional Chinese Medicine Pharmacology,Beijing 100091,China;Beijing University of Chinese Medicine,Beijing 100029,China)

机构地区：[1]中国中医科学院西苑医院基础医学研究所/中药药理北京市重点实验室,北京100091 [2]北京中医药大学,北京100029

出　　处：《中华中医药杂志》2022年第8期4454-4458,共5页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家重大新药创制专项(No.2017ZX09301018)。

摘　　要：目的:利用单侧输尿管梗阻(UUO)模型探讨芪术颗粒通过调控PI3K/AKT/GSK3β/MAPK信号通路延缓肾脏纤维化进展的机制。方法:将28只雄性C57BL/6小鼠随机分为假手术组、模型组、芪术颗粒组、贝那普利组,每组7只。模型组及两个治疗组行左侧输尿管结扎,假手术组仅单纯分离不结扎。术后1 d开始灌胃相应药物,连续灌胃14 d后取材,检测各组血肌酐(Scr)、尿素氮(BUN)水平,通过HE和Masson染色观察结扎侧肾组织病理变化,Western Blot检测p-AKT、AKT、GSK3β、p38-MAPK蛋白表达水平。结果:与假手术组比较,模型组Scr、BUN水平及肾组织p-AKT、AKT、GSK3β、p38-MAPK蛋白表达水平均显著升高(P<0.01),肾组织病理见肾间质大量胶原纤维沉积;与模型组比较,芪术颗粒组和贝那普利组上述各项指标均显著降低(P<0.01,P<0.05),肾组织病理见肾间质胶原纤维沉积减少。结论:芪术颗粒可能通过PI3K/AKT/GSK3β/MAPK信号通路发挥保护肾功能、延缓肾纤维化进展的作用。Objective:The unilateral ureteral obstruction(UUO) model was used to explore the mechanism of Qizhu Granules delaying the progression of renal fibrosis by regulating the PI3K/AKT/GSK3β/MAPK signaling pathway.Methods:A total of 28 male C57BL/6 mice were randomly divided into sham group,model group,Qizhu Granules group and benazepril group,7 mice in each group.The left ureter was ligated in the model and each treatment groups.In the sham group,the left ureter was not ligated.Mouse was gavage from first day after surgery.After 14 days of continuous gavage,blood samples were taken to detect serum creatinine(Scr) and blood urea nitrogen(BUN).The kidney tissue of ligation side was taken to observe the pathological change by HE and Masson staining,and detected the expression levels of p-AKT,AKT,GSK3β,and p38-MAPK protein by Western Blot.Results:Compared with the sham group,the Scr,BUN and p-AKT,AKT,GSK3β,p38-MAPK proteins in the model group were significantly increased(P<0.01);renal tissue pathology showed a large amount of collagen fiber deposition in the renal interstitium.Compared with the model group,the above indicators in the Qizhu Granules and benazepril group were significantly decreased(P<0.05,P<0.01),and renal tissue pathology showed collagen fiber deposition in the renal interstitium also were reduced.Conclusion:Qizhu Granules may play a role of protecting renal function and delaying the progression of renal fibrosis through PI3K/AKT/GSK3β/MAPK signaling pathway.

关 键 词：芪术颗粒 肾纤维化 PI3K AKT GSK3Β MAPK 

分 类 号：R285.5[医药卫生—中药学]