中国药理学通报2024，Vol.40Issue(8)：1552-1558,7.DOI:10.12360/CPB202311055
基于NLRP3/caspase-1/GSDMD信号通路介导的细胞焦亡探讨大黄糖络丸对糖尿病肾脏疾病的干预效应
The intervention effect of Dahuang Tangluo Pills on diabetic kidney disease based on NLRP3/caspase-1/GSDMD pathway mediated pyroptosis
摘要
Abstract
Aim To investigate the effect of Dahuang Tangluo pills(DHTL)on NOD-like receptor protein 3(NLRP3)/cysteine aspartate proteolytic enzyme-1(caspase-1)/apodermic D(GSDMD)pathway-media-ted pyroptosis in db/db mice with diabetic kidney dis-ease(DKD)and the underlying mechanism.Methods Eight db/m mice were selected as control group,and forty db/db mice were randomly divided into mod-el group,low dose group,medium dose group,high dose group and dapagliflozin group,with eight mice in each group.The control group and model group were given equal volume normal saline intragastric adminis-tration,the low,medium and high dose groups were given DHTL solution of 0.9,1.8 and 3.6 mg·kg-1,respectively,and the dapagliflozin group was given dapagliflozin tablet solution of 1.5 mg·kg-1,and the six groups were given intragastric administration once a day for 10 weeks.The body weight of mice was meas-ured daily and the dose was adjusted during adminis-tration.Fasting blood glucose(FBG)and body weight were measured after administration.The levels of 24-hour urinary total protein(24h-UTP),blood creatinine(Scr)and urea nitrogen(BUN)were measured by au-tomatic biochemical analyzer.The levels of interleukin-1 β(IL-1β),interleukin-6(IL-6),interleukin-18(IL-18)and tumor necrosis factor-α(TNF-α)in re-nal tissue of mice were determined by enzyme-linked immunosorbent assay(ELISA).The pathological changes of renal tissue were observed by hematoxylin-eosin(HE)staining.The DNA damage in mouse kid-ney tissue was observed using in situ end labeling(TUNEL)staining.The mRNA and protein expres-sions of NLRP3,caspase-1 and GSDMD in mouse kid-ney tissues were detected by Real-time quantitative PCR and Western blot.Results Compared with the control group,FBG,body weight,IL-1β,IL-6,IL-18 and TNF-α in the model group significantly increased(P＜0.01).The mRNA and protein expressions of NLRP3,caspase-1 and GSDMD in mouse kidney tis-sues significantly increased(P＜0.01).Compared with the model group,the levels of FBG,body weight,IL-1β,IL-6,IL-18 and TNF-α in each administration group significantly decreased(P＜0.05).The patho-logical morphology of renal tissue was improved in dif-ferent degrees,and the number of positive cells in re-nal tissue was significantly reduced(P＜0.05).The mRNA and protein expressions of NLRP3,caspase-1 and GSDMD in renal tissue of mice in high and medi-um dose of DHTL and dapagliflozin group significantly decreased(P＜0.05).Conclusions DHTL can im-prove the renal injury of DKD,and its mechanism may be through the regulation of NLRP3/caspase-1/GSD-MD pathway to inhibit pyroptosis and relieve the in-flammatory response of DKD mice.关键词
糖尿病肾脏疾病/大黄糖络丸/NLRP3/caspase-1/GSDMD/细胞焦亡/炎症反应Key words
diabetic kidney disease/Dahuang Tan-gluo pills/NLRP3/caspase-1/GSDMD/pyroptosis/in-flammatory response分类
医药卫生引用本文复制引用
薛春霞,张媛媛,杨霞,章溥,苏蓓蓓,朱向东,梁建庆..基于NLRP3/caspase-1/GSDMD信号通路介导的细胞焦亡探讨大黄糖络丸对糖尿病肾脏疾病的干预效应[J].中国药理学通报,2024,40(8):1552-1558,7.基金项目
国家自然科学基金资助项目(No 82160929) （No 82160929）
甘肃省科技厅第十一批省级科技计划自然科学基金项目(No 21JR11RA143) （No 21JR11RA143）
敦煌医学与转化教育部重点实验室开放课题(No DHYX18-08) （No DHYX18-08）
中医学一级学科"岐黄英才"导师专项基金硕导项目(No ZYXKSD-202211) （No ZYXKSD-202211）
甘肃省教育科技创新项目(No 2021CYZC-03) （No 2021CYZC-03）
