基于NLRP3炎症小体介导的细胞焦亡探讨丹蛭降糖胶囊对db/db小鼠心肌损伤的影响  

Effects of Danzhi Jiangtang capsules on myocardial injury of db/db mice based on NLRP3 inflammasome-mediated pyroptosis

作　　者：阮诺冰 李金菊 许奇 经加吻 高家荣[2] 方朝晖[2,3,4] RUAN Nuo-bing;LI Jin-ju;XU Qi;JING Jia-wen;GAO Jia-rong;FANG Zhao-hui(the First Clinical Medical College,Anhui University of Chinese Medicine,Hefei 230038,China;the First Affiliated Hospital,Anhui University of Chinese Medicine,Hefei 230031,China;KeyLaboratory of Xin′an Medicine,Ministry of Education(Anhui University of Chinese Medicine),Hefei 230038,China;Center for Xin′an Medicine and Modernization of Traditional Chinese Medicine,Institute of Health Research,Hefei Comprehensive National Science Center,Hefei 230012,China)

机构地区：[1]安徽中医药大学第一临床医学院,安徽合肥230038 [2]安徽中医药大学第一附属医院,安徽合肥230031 [3]新安医学教育部重点实验室(安徽中医药大学),安徽合肥230038 [4]合肥综合性国家科学中心大健康研究院新安医学与中医药现代化研究所,安徽合肥230012

出　　处：《中国药理学通报》2025年第4期786-792,共7页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No.82174153);2型糖尿病中医药循证能力提升项目(No.2023-24);合肥综合性国家科学中心大健康研究院“揭榜挂帅”项目(No.2023 CXMMTCM003)。

摘　　要：目的基于NLRP3炎症小体介导的细胞焦亡,探讨丹蛭降糖胶囊(Danzhi Jiangtang capsules,DJC)对db/db小鼠心肌保护作用的可能机制。方法将db/db小鼠随机分为模型组、DJC低、中、高剂量组及二甲双胍组,另取db/m小鼠为对照组,连续给药8周。给药结束后,检测各组小鼠血糖、血脂、心肌酶指标及炎症因子水平;HE及Masson染色观察心肌组织形态及纤维化情况;TUNEL染色检测细胞凋亡情况;RT-qPCR检测心肌组织ANP、BNP、β-MHC mRNA表达情况;Western blot检测心肌组织NLRP3、ASC、caspase-1、cleavedcaspase-1、GSDMD和GSDMD-NT蛋白表达情况。结果DJC能减轻db/db小鼠心肌病理损伤,减少胶原沉积和细胞凋亡,降低血糖、血脂、心肌酶和炎症因子水平,降低心肌组织中ANP、BNP、β-MHC mRNA表达,以及NLRP3、ASC、caspase-1、cleavedcaspase-1、GSDMD、GSDMD-NT蛋白表达。结论DJC可减轻db/db小鼠心肌损伤,其可能是通过抑制NLRP3炎症小体的激活,减轻心肌细胞焦亡,改善炎症状态来发挥作用。Aim To investigate the possible mechanism of the myocardial protective effect of Danzhi Jiangtang capsules(DJC)on db/db mice based on NLRP3 inflammasome-mediated pyroptosis.Methods The db/db mice were randomly divided into the model group,DJC low,medium,and high dose groups,and the metformin group,and the db/m mice were taken as the blank group.The administration lasted for eightweeks.At the end of drug administration,blood glucose,blood lipids,cardiac enzymes and inflammatory factors were detected in each group of mice.HE and Masson staining was performed to observe the morphology and fibrosis of myocardial tissue.TUNEL staining was performed to detect apoptosis.RT-qPCR was performed to detect the mRNA expression of ANP,BNP andβ-MHC,and Western blot was performed to detect the protein expression of NLRP3,ASC,caspase-1,cleavedcaspase-1,GSDMD and GSDMD-NT in myocardial tissue.Results DJC could alleviate myocardial pathological damage,reduce collagen deposition and apoptosis,reduce the levels of blood glucose,blood lipid,myocardial enzyme and inflammatory factors in db/db mice.DJC could reduce the mRNA expressions of ANP,BNP andβ-MHC,and the protein expressions of NLRP3,ASC,caspase-1,cleavedcaspase-1,GSDMD and GSDMD-NT in myocardial tissues.Conclusion DJC attenuates myocardial injury in db/db mice,probably by inhibiting the activation of NLRP3 inflammasomes,attenuating cardiomyocyte pyroptosis,and ameliorating the inflammatory state.

关 键 词：丹蛭降糖胶囊 糖尿病心肌病 DB/DB小鼠 NLRP3炎症小体 细胞焦亡 心肌损伤 

分 类 号：R-332[医药卫生] R285.5R322.11R364.5R542.2R587.1