摘要
目的探究利拉鲁肽对糖尿病肾病大鼠的作用及其调控机制。方法采取多次小剂量ip链脲佐菌素40 mg/kg构建糖尿病肾病大鼠模型,分为模型组、利拉鲁肽组、活性氧簇(ROS)抑制剂(NAC)组、利拉鲁肽+NAC组,另设置对照组,每组10只。利拉鲁肽组大鼠sc 200μg/(kg·d)的利拉鲁肽;NAC组大鼠ip 20 mg/(kg·d)的NAC;利拉鲁肽+NAC组大鼠sc 200μg/(kg·d)的利拉鲁肽的同时ip 20 mg/(kg·d)的NAC;对照组和模型组大鼠sc等量的生理盐水,1次/d,连续治疗4周。全自动分析仪检测24 h尿微量蛋白排泄率(MAER);血糖仪测定空腹血糖(FBG);试剂盒检测血清肌酐(Scr)、尿素氮(BUN)水平;HE染色、Masson染色观察肾组织病理变化;二氢乙锭(DHE)荧光探针检测肾组织活性氧(ROS)水平;化学比色法检测肾组织丙二醛(MDA)含量、谷胱甘肽过氧化物酶(GSH)和超氧化物歧化酶(SOD)活性;Western blotting检测肾组织NOD样受体蛋白3(NLRP3)炎症小体和焦亡相关蛋白表达。结果与模型组相比,利拉鲁肽组和NAC组大鼠MAER、Scr、BUN、FBG均显著降低(P<0.05);肾组织ROS、MDA含量显著降低,GSH、SOD活性升高(P<0.05);NLRP3炎症小体相关蛋白[NLRP3、凋亡相关斑点样蛋白(ASC)、Caspase-1]和焦亡相关蛋白[cleaved-Caspase-1、GSDMDN、白细胞介素(IL)-1β、IL-18]表达均显著降低(P<0.05、0.01)。与利拉鲁肽组相比,利拉鲁肽+NAC组上述指标均得到进一步改善,肾组织病理损伤进一步减轻。结论利拉鲁肽能够通过ROS-NLRP3炎症小体途径抑制肾组织氧化应激介导的NLRP3炎症小体活化,从而抑制细胞焦亡,并最终发挥抗糖尿病肾病肾损伤作用。
Objective To investigate the effect of liraglutide on diabetic nephropathy in rats and its regulatory mechanism.Methods The diabetic nephropathy rat model was constructed with multiple low-dose streptozocin 40 mg/kg,and was divided into model group,liraglutide group,ROS inhibitor(NAC)group,liraglutide+NAC group,and control group,with 10 rats in each group.Liraglutide group rats sc 200μg/(kgd)liraglutide,NAC group rats ip 20 mg/(kgd)NAC,liraglutide+NAC group was sc 200μg/(kgd)of liraglutide and ip 20 mg/(kgd)of NAC.Rats in control group and model group were treated with sc equal amount of normal saline once daily for 4 weeks.24 h MAER was measured by automatic analyzer.FBG was measured by glucose meter.Scr and BUN levels were detected with the kit.The pathological changes of renal tissue were observed by HE staining and Masson staining.DHE fluorescent probe was used to detect ROS in renal tissue.The content of MDA and the activities of GSH and SOD were detected by chemical colorimetry.Expression of NLRP3 inflammasome and pyroptosis related protein were detected by Western blotting.Results Compared with model group,MAER,Scr,BUN and FBG in liraglutide group and NAC group were significantly decreased(P<0.05).The contents of ROS and MDA in renal tissue were significantly decreased,while the activities of GSH and SOD were increased(P<0.05).Expressions of NLRP3 inflammator-associated proteins(NLRP3,ASC,Caspase-1)and pyro related proteins(cleaved Caspase-1,GSDMD-N,IL-1β,IL-18)were significantly decreased(P<0.05,0.01).Compared with liraglutide group,the above indexes were further improved in liraglutide+NAC group,and the pathological injury of kidney tissue was further alleviated.Conclusion Liraglutide can inhibit the activation of NLRP3 inflammasome mediated by oxidative stress in renal tissue through ROS-NLRP3 inflammasome pathway,thereby inhibiting pyroptosis,and finally playing an anti diabetic nephropathy renal injury role.
作者
王卓怡
陆筱波
WANG Zhuo-yi;LU Xiao-bo(Department of Pharmacy,Zhangjiagang Traditional Chinese Medicine Hospital,Zhangjiagang 215600,China)
出处
《现代药物与临床》
CAS
2023年第9期2126-2132,共7页
Drugs & Clinic
