陕西医学杂志2025，Vol.54Issue(10)：1324-1330,7.DOI:10.3969/j.issn.1000-7377.2025.10.005
秋水仙碱对动脉粥样硬化小鼠主动脉斑块的干预作用及对核苷酸结合寡聚化结构域样受体3/含CARD结构域的凋亡相关颗粒样蛋白/含半胱氨酸的天冬氨酸蛋白酶1信号通路、炎症反应的影响
Intervention effect of colchicine on aortic plaque in atherosclerosis mice and the influence on NLRP3/ASC/Caspase-1 signal pathway and inflammatory response
摘要
Abstract
Objective:To explore the intervention effect of colchicine on aortic plaque in Atherosclerosis(AS)mice,and analyze its effects on inflammatory reaction,nucleotide binding oligomeric domain like receptor 3(NLRP3)/apoptosis related granule like protein(ASC)containing CARD domain/Caspase-1 signaling pathway.Methods:Twelve normal mice served as the blank control group,and 48 mice of the same strain were randomly divid-ed into the model group,colchicine-L group,colchicine-M group,and colchicine-H group,with 12 mice in each group.The pathological changes of aortic plaques,the severity of aortic plaque lesions,the non-alcoholic steatohepatitis activ-ity score(NAS),the cross-sectional area of epididymal fat,as well as the levels of blood lipids,blood glucose,athero-sclerosis index(AI),inflammatory markers,oxidative stress markers,and the NLRP3/ASC/Caspase-1 signaling pathway(NLRP3 mRNA,ASC mRNA,Caspase-1 mRNA,and protein)were compared among the groups.Results:Compared with the model group,the colchicine-L(low-dose),colchicine-M(medium-dose),and colchicine-H(high-dose)groups showed dose-dependent reductions in the following parameters(all P＜0.05).Compared with the model group,the levels of serum total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),fasting blood glucose(FPG),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),monocyte chemoat-tractant protein-1(MCP-1),intercellular adhesion molecule-1(ICAM-1),vascular cell adhesion molecule-1(VCAM-1),high-sensitivity C-reactive protein(hs CRP),malondialdehyde(MDA),oxidized low-density lipoprotein(ox LDL),insulin resistance index(HOMA-IR),and AI were reduced in the colchicine-L group,colchicine-M group,and colchi-cine-H group.Serum superoxide dismutase levels were also reduced.The levels of superoxide dismutase(SOD)and glutathione peroxidase(GSH px)increased in a dose-dependent manner(all P＜0.05).Compared with the model group,the levels of NLRP3 mRNA,ASC mRNA,Caspase-1 mRNA,and protein in the colchicine-L group,colchicine-M group,and colchicine-H group decreased in a dose-dependent manner(all P＜0.05).Conclusion:Colchicine has a good intervention effect on aortic plaques in AS mice,which can improve the severity of AS lesions,reduce blood lipid and blood glucose levels,alleviate vascular inflammatory responses,and mitigate oxidative stress responses.Its mech-anism of action may be related to the inhibition of NLRP3/ASC/Caspase-l signaling pathway activation.关键词
秋水仙碱/动脉粥样硬化/主动脉斑块/炎症反应/核苷酸结合寡聚化结构域样受体3/含CARD结构域的凋亡相关颗粒样蛋白/含半胱氨酸的天冬氨酸蛋白酶1Key words
Colchicine/Atherosclerosis/Aortic plaque/Inflammatory response/Nucleotide binding oligomeriza-tion domain like receptor 3/Apoptosis related granule like proteins containing CARD domains/Aspartate protease 1 containing cysteine分类
医药卫生引用本文复制引用
谢佳佳,廖文君,吴碧君,赵振华..秋水仙碱对动脉粥样硬化小鼠主动脉斑块的干预作用及对核苷酸结合寡聚化结构域样受体3/含CARD结构域的凋亡相关颗粒样蛋白/含半胱氨酸的天冬氨酸蛋白酶1信号通路、炎症反应的影响[J].陕西医学杂志,2025,54(10):1324-1330,7.基金项目
广东省自然科学基金资助项目(2021A1515010384) （2021A1515010384）
广州市科技计划项目(2023A03J0252) （2023A03J0252）
