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作 者:罗阳燕 高芳[1] 魏梦婷 毛楠[1] LUO Yangyan;GAO Fang;WEI Mengting(Department of Nephrology,First Affiliated Hospital of Chengdu Medical College,Chengdu,610500)
机构地区:[1]成都医学院第一附属医院肾病科,成都610500
出 处:《中国中西医结合肾病杂志》2022年第9期764-767,I0002,共5页Chinese Journal of Integrated Traditional and Western Nephrology
基 金:四川省医学科研青年创新项目(No.Q17024);成都医学院第一附属医院独立资助项目(No.CYFY15DL-07)。
摘 要:目的:探究鸢尾素对糖尿病肾病(DN)大鼠丝裂原活化蛋白激酶p38(p38 MAPK)/核因子-κB(NF-κB)通路及肾损伤的影响。方法:SPF级SD雄性大鼠随机选取6只为对照组。造模成功后,分为对照组、模型组、厄洛替尼组、低中高剂量鸢尾素组(n=6)。给药结束后腹主动脉抽血检测各组大鼠血清空腹血糖(FBG)、血肌酐(Scr)及24 h尿蛋白含量,处死大鼠,观察各组大鼠肾脏组织病理学变化,检测大鼠肾脏组织中p38 MAPK、NF-κB、基质金属蛋白酶-9(MMP-9)及肿瘤坏死因子-α(TNF-α)mRNA的水平、p38 MAPK、NF-κB、MMP-9和TNF-α蛋白水平。结果:与对照组相比,模型组大鼠血清FBG、Scr及24 h尿蛋白水平升高,并出现肾小球肿胀、硬化和间质纤维化现象,肾脏中p38 MAPK、NF-κB、MMP-9、TNF-αmRNA及蛋白水平升高(P<0.05);与模型组相比,厄洛替尼组、低中高剂量鸢尾素组血清FBG、Scr及24 h尿蛋白水平降低,肾小球肥大、肾小球硬化和胶原沉积程度逐渐减轻,肾脏中p38 MAPK、NF-κB、MMP-9及TNF-αmRNA及蛋白水平降低(P<0.05)。结论:鸢尾素可能通过抑制p38 MAPK/NF-κB通路表达,降低肾小球炎症及纤维化水平,达到改善DN的目的,可能作为DN潜在的治疗药物。Objective:To investigate the effects of irisin on mitogen activated protein kinase p38(p38 MAPK)/nuclear factor-κB(NF-κB)pathway and renal injury in diabetic nephropathy(DN)rats.Methods:Six SPF male SD rats were randomly selected as the control group.After successful modeling,the rats were divided into control group,model group,erlotinib group and low,medium and high dose irisin groups(n=6).At the end of administration,blood samples were drawn from abdominal aorta to detect the levels of fasting blood glucose(FBG),serum creatinine(Scr)and 24 h urinary protein,the rats were killed,the histopathological changes of kidney were observed,the mRNA levels of p38 MAPK,NF-κB,matrix metalloproteinase-9(MMP-9)and tumor necrosis factor-α(TNF-α),the protein levels of p38 MAPK,NF-κB,MMP-9 and TNF-αwere detected.Results:Compared with those in the control group,the levels of serum FBG,Scr and 24 h urinary protein in the model group were higher,and glomerular swelling,sclerosis and interstitial fibrosis were observed,the mRNA and protein levels of p38 MAPK,NF-κB,MMP-9 and TNF-αin kidney were higher(P<0.05);compared with those in the model group,the levels of serum FBG,Scr and 24 h urinary protein in the model group were lower,the degree of glomerular hypertrophy,glomerulosclerosis and collagen deposition gradually decreased,the mRNA and protein levels of p38 MAPK,NF-κB,MMP-9 and TNF-αin kidney were lower(P<0.05).Conclusion:Irisin may reduce glomerular inflammation and fibrosis by inhibiting the expression of p38 MAPK/NF-κB pathway,so as to improve DN,which may be a potential therapeutic drug for DN.
关 键 词:糖尿病肾病 鸢尾素 丝裂原活化蛋白激酶P38 核因子-ΚB
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