南方医科大学学报2025，Vol.45Issue(5)：977-985,9.DOI:10.12122/j.issn.1673-4254.2025.05.10
积雪草苷通过抑制NLRP3炎症体介导的细胞焦亡减轻大鼠心肌缺血再灌注损伤
Asiaticoside alleviates myocardial ischemia-reperfusion injury in rats by inhibiting NLRP3 inflammasome-mediated pyroptosis
摘要
Abstract
Objective To study the mechanism mediating the protective effect of asiaticoside(AS)against myocardial ischemia-reperfusion injury(MIRI)in rats.Methods Fifty SD rats were randomized into sham-operated group,MIRI model group and AS treatment group.AS treatment was administered at low,moderate and high doses by daily gavage for 2 weeks before MIRI modeling(n=10).Serum levels of lactate dehydrogenase(LDH),creatine kinase isoenzyme(CK-MB),interleukin-18(IL-18)and IL-1β,the volume of myocardial infarction and ischemia,and myocardial pathologies of the rats were determined or observed.The protein expression levels of NLRP3,ASC,caspase-1,GSDMD,GSDMD-N,IL-1β and IL-18 in the myocardial tissues were detected using Western blotting.The changes in the expression levels of these proteins were also detected in H9C2 cells with AS pretreatment prior to hypoxia-reoxygenation(H/R)injury.Results The rats models of MIRI exhibited significant myocardial infarction and ischemia with increased serum levels of LDH and CK-MB and myocardial expressions of NLRP3,ASC,caspase-1,GSDMD,GSDMD-N,IL-1β and IL-18.AS pretreatment effectively reduced myocardial infarction volume in the rat models and significantly reduced serum LDH and CK-MB levels and the protein levels in the myocardial tissue in a dose-dependent manner.In the H9C2 cell model of H/R injury,AS pretreatment significantly suppressed the elevation of the protein expressions of NLRP3,ASC,caspase-1,GSDMD,GSDMD-N,IL-1β and IL-18.Molecular docking studies showed that AS had a strong binding affinity with NLRP3.Conclusion Asiaticoside can alleviate MIRI in rats possibly by inhibiting NLRP3 inflammasome-mediated pyroptosis.关键词
积雪草苷/心肌缺血再灌注损伤/NLRP3/细胞焦亡Key words
asiaticoside/myocardial ischemia-reperfusion injury/NLRP3/pyroptosis引用本文复制引用
卞芬兰,倪诗垚,赵鹏,戚毛男星,唐碧,王洪巨,康品方,刘进军..积雪草苷通过抑制NLRP3炎症体介导的细胞焦亡减轻大鼠心肌缺血再灌注损伤[J].南方医科大学学报,2025,45(5):977-985,9.基金项目
国家自然科学基金(81970313) （81970313）
安徽省自然科学基金(2208085MH192) （2208085MH192）
安徽省高校协同创新项目(GXXT-2020-019) （GXXT-2020-019）
安徽省优秀青年基金(2022AH030141) （2022AH030141）
安徽省优秀创新团队(2022AH010083) （2022AH010083）
蚌埠医学院研究生科研创新计划项目(Byycx24021) （Byycx24021）
安徽省临床转化课题青年项目(202304295107020087)Supported by National Natural Science Foundation of China(81970313). （202304295107020087）
