摘要
目的探讨细胞焦亡在心肌缺血/再灌注损伤中的作用及机制。方法将75只SD大鼠随机分为对照组、缺血/再灌注组、YVAD组、YVAD+缺血/再灌注组、MCC950组、MCC950+缺血/再灌注组。其中对照组、YVAD组、MCC950组分别为10只,其余各组分别为15只。在建立心肌缺血/再灌注损伤的大鼠模型过程中,缺血/再灌注组、YVAD+缺血/再灌注组、MCC950+缺血/再灌注组各死亡1~4只。检测对照组、缺血/再灌注组心肌组织中Tunel染色阳性率,NLRP3炎症小体、caspase-1、IL-1β及GSDMD-N表达情况。检测对照组、YVAD组、缺血/再灌注组和YVAD+缺血/再灌注组的Tunel染色阳性率、心肌梗死面积、Caspase-1、IL-1β及GSDMD-N表达情况。最后检测对照组、MCC950组、缺血/再灌注组和MCC950+缺血/再灌注组Tunel染色阳性率、心肌梗死面积、Caspase-1、IL-1β及GSDMD-N表达。结果缺血/再灌注后心肌细胞焦亡情况:缺血/再灌注组Tunel染色阳性率、心肌梗死面积、NLRP3、Caspase-1、IL-1β及GSDMD-N的表达明显高于对照组(均P<0.05)。干预焦亡后的情况:YVAD+缺血/再灌注组Tunel染色阳性率、心肌梗死面积、Caspase-1(成熟体)、IL-1β及GSDMD-N的表达均高于对照组,明显低于缺血/再灌注组(均P<0.05)。抑制NLRP3表达后的情况:MCC950+缺血/再灌注组Tunel染色阳性率、心肌梗死面积、Caspase-1、IL-1β及GSDMD-N表达水平虽高于对照组,明显低于缺血/再灌注组(均P<0.05)。结论大鼠心肌的缺血/再灌注损伤与NLRP3炎症小体介导的细胞焦亡有关。
Objective To investigate the role and the possible mechanism of pyroptosis in ischemia/reperfusion(I/R)-injury.Methods 75 male SD rats were randomly divided into Control group,I/R group(underwent I/R-treatment),YVAD group(pretreated with Z-YVAD-FMK),YVAD+I/R group(pretreated with Z-YVAD-FMK before I/R-treatment),MCC950 group(pretreated with MCC950)and MCC950+I/R group(pretreated with MCC950 before I/R-treatment).In order to observe whether I/R-treatment could cause pyroptosis,the positive rate of Tunel staining,the expression of NLRP3 inflammasomes,caspase-1,IL-1βand GSDMD-N in the each groups were detected.Results The positive rate of TUNEL staining,infarct size,the expression of NLRP 3,caspase 1,IL 1βand GSDMD n in ischemia/reperfusion group were significantly higher than those in control group(all P<0.05).The positive rate of TUNEL staining,infarct size,expression of caspase 1(mature body),IL-1βand GSDMD n in YVAD+I/R group were higher than those in control group,but lower than those in I/R group(all P<0.05).After inhibition of NLRP3 expression,the positive rate of TUNEL staining,myocardial infarction size,caspase 1,IL-1βand GSDMD n expression levels in MCC950+I/R group were higher than those in control group,but significantly lower than those in I/R group(all P<0.05).Conclusion Myocardial ischemia/reperfusion injury in rats is related to NLRP3 inflammasome mediated pyroptosis.
作者
岳荣川
卢圣忠
罗瑜
杨小利
王小波
秦丹
郑在勇
吕明明
胡厚祥
YUE Rongchuan;LU Shengzhong;LUO Yu;YANG Xiaoli;WANG Xiaobo;QIN Dan;ZHENG Zaiyong;LYU Mingming;HU Houxiang(Department of Cardiology, The Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan, China;Department of Cardiology, Daping Hospital, Army Medical University, Chongqing 400042, China)
出处
《西部医学》
2021年第3期330-335,共6页
Medical Journal of West China
基金
国家自然科学基金(81600232)
南充市市校科技战略合作专项(NSMC20170210,18SXHZ0458)
四川省教育厅重点项目(17ZA0183)
川北医学院博士科研启动基金(CBY15-QD12)。
