摘要
目的探究恩格列净通过Caspase-1介导的细胞焦亡对血糖波动糖尿病小鼠肾损伤的影响。方法将30只SPF级SD雄性小鼠随机分为对照组、血糖波动组及恩格列净组,每组10只。恩格列净组、血糖波动组小鼠成功复制血糖波动糖尿病模型后,分别同时间给予恩格列净10 mg/(kg·d)、等量生理盐水灌胃,1次/d,连续4周;对照组小鼠同时间灌胃等量生理盐水。采用全自动生化分析仪测定24 h尿蛋白、血肌酐、血尿素氮水平,苏木精-伊红(HE)染色观察肾组织病理学变化,酶联免疫吸附试验测定肾脏组织白细胞介素1β(IL-1β)水平,Western blotting检测肾组织NLRP3、Cleaved caspase-1、GSDMD-N蛋白表达。结果与对照组比较,血糖波动组小鼠肾小球体积增大,毛细血管基底膜明显增厚,系膜基质增生,肾小管上皮细胞中可见空泡化。与血糖波动组比较,恩格列净组小鼠上述病理变化有所改善。与对照组比较,血糖波动组和恩格列净组小鼠24 h尿蛋白、血尿素氮、血肌酐、肾组织IL-8,以及NLRP3、Cleaved caspase-1、GSDMD-N蛋白相对表达量升高(P<0.05),但恩格列净组小鼠24 h尿蛋白、血尿素氮、血肌酐、肾组织IL-1β,以及NLRP3、Cleaved caspase-1、GSDMD-N蛋白相对表达量低于血糖波动组(P<0.05)。结论恩格列净可能通过抑制Caspase-1通路活化,对血糖波动性糖尿病小鼠肾损伤发挥保护作用。
Objective To explore the effects of empagliflozin on renal injury in diabetic mice with blood glucose fluctuation via pyroptosis mediated by Caspase-1.Methods Thirty SPF male SD mice were randomly divided into control group,blood glucose fluctuation group and empagliflozin group,each group with 10 mice.After the modeling of diabetes mellitus with blood glucose fluctuation,the mice in the blood glucose fluctuation group and the empagliflozin group were given 10 mg/(kg·d)of empagliflozin or the equal volume of normal saline by gavage once a day for 4 weeks.The mice in the control group were also given the equal volume of normal saline at the same time.The levels of 24-h urine protein,blood creatinine and blood urea nitrogen were measured by automatic biochemical analyzer.Hematoxylin and eosin(HE)staining was used to observe the pathological changes of renal tissues.The level of interleukin-1β(IL-1β)in renal tissues was determined by enzyme-linked immunosorbent assay.The protein levels of NOD-like receptor family pyrin domain-containing 3(NLRP3),Cleaved caspase-1 and GSDMD-N in renal tissues were measured by Western blotting.Results Compared with the control group,increased glomerular volume,obvious thickening of glomerular basement membrane,mesangial matrix hyperplasia and vacuolation in renal tubular epithelium were observed in the blood glucose fluctuation group,while these pathological changes were ameliorated in the empagliflozin group relative to the blood glucose fluctuation group.In addition,the levels of 24-h urine protein,blood urea nitrogen,blood creatinine,IL-1β,and the protein levels of NLRP3,Cleaved caspase-1 and GSDMD-N were higher in the blood glucose fluctuation group and empagliflozin group compared with the control group(P<0.05),but they were even lower in the empagliflozin group than those in the blood glucose fluctuation group(P<0.05).Conclusions Empagliflozin may play a protective role in renal injury in diabetic mice with blood glucose fluctuation by inhibiting the activation of Caspase-1 pathway.
作者
史丽
胡婷婷
李红
张三明
刘智慧
左惠玲
胡利梅
任卫东
Li Shi;Ting-ting Hu;Hong Li;San-ming Zhang;Zhi-hui Liu;Hui-ling Zuo;Li-mei Hu;Wei-dong Ren(Department of Endocrinology,The First Affiliated Hospital of Hebei North University,Zhangjiakou,Hebei 075000,China;International Medical Services,The First Affiliated Hospital of Hebei North University,Zhangjiakou,Hebei 075000,China;Zhangjiakou Municipal Health Commission,Zhangjiakou,Hebei 075000,China;Department of Nuclear Medicine,The First Affiliated Hospital of Hebei North University,Zhangjiakou,Hebei 075000,China)
出处
《中国现代医学杂志》
CAS
北大核心
2022年第4期40-44,共5页
China Journal of Modern Medicine
基金
2021年度河北省“三三三人才工程”(No:A202103006)
张家口市科技攻关计划项目(No:2021040D)。
关键词
糖尿病
肾损伤
血糖波动
恩格列净
半胱天冬酶-1通路
焦亡
diabetes mellitus
renal injury
blood glucose fluctuation
empagliflozin
Caspase-1 pathway
py‐roptosis
