lncRNA MALAT1/HMGB1在缺血后处理减轻缺血再灌注损伤中的作用
Role of lncRNA MALAT1/HMGB1 in post-ischemic treatment to alliveate ischemia-reperfusion injury
王高尚1
作者信息
- 1. 郑州市第七人民医院心内科,河南郑州 450017
- 折叠
摘要
目的 探讨长链非编码RNA(long non-coding RNA,lncRNA)肺腺癌转录子1(MALAT1)以及下游调控蛋白高迁移率族蛋白B1(High-mobility group protein box-1,HMGB1)在缺血后处理降低大鼠心肌缺血-再灌注损伤(ischemia/reperfusion injury,IRI)中的作用.方法 将24只大鼠饲养7天后,随机分成3组:假手术(Sham)组、缺血再灌注(ischemia/reperfusion,IR)组、缺血后处理(ischemic post-conditioning,IPO)组.模型构建完毕 24 h 进行检测大鼠血清中心肌肌钙蛋白Ⅰ(cTnⅠ)和白介素6(IL-6)表达水平,取材检测大鼠心肌梗死面积,检测大鼠心肌组织中MALAT1转录表达水平的差异,HMGB1、Toll样受体4(Toll-like receptor4,TLR4)蛋白含量差异.结果 与Sham组比较,IR、IPO组血清中cTnⅠ、IL-6水平明显升高,心肌梗死面积明显增加,心肌组织中MALAT1表达水平显著上调,HMGB1、TLR4水平明显升高(P＜0.05).与IR组比较,IPO组cTnⅠ浓度显著降低,心肌梗死面积显著减小,心肌组织中lncRNA-MALAT1相对表达量降低,HMGB1、TLR4蛋白含量降低(P＜0.05).结论 及时的缺血后处理可有效减缓大鼠心肌缺血-再灌注的损伤程度,其相关机制可能与抑制MALAT1调节控制HMGB1、TLR4表达水平之间有一定的关联.
Abstract
Objective To investigate the role of long chain non-coding RNA(lncRNA)lung adenocarcinoma tran-script 1(MALAT1)and the downstream regulatory protein,high mobility group protein B1(HMGB1),in the alleviation of myocardial ischemia-reperfusion injury(MIRI)by ischemic post-treatment in rats.Methods After 7 days of acclima-tisation,24 male SD rats were randomly divided into three groups:sham operation(Sham)group,ischemia-reperfusion(IR)group,and ischemia post-treatment(IPO)group.The serum levels of cardiac troponin Ⅰ(cTnⅠ)and interleukin 6(IL-6)were measured at 24 h after model construction,and the myocardial infarction area was detected by sampling;the differences in the expression of MALAT1,the protein content of HMGB1,and the protein content of Toll-like receptor 4(TLR4)were detected in the myocardial tissues of rats.Results Compared with the Sham group,the serum concen-trations of cTnT and IL-6 in the IR and IPO groups were significantly higher,the myocardial infarction area was signifi-cantly larger,the relative expression of lncRNA-MALAT1 in myocardial tissues was significantly higher,and the pro-tein contents of HMGB1 and TLR4 were significantly higher(P＜0.05).Compared with the IR group,cTnⅠ concentra-tion in the IPO group was significantly reduced,myocardial infarction area was significantly reduced,relative expression of lncRNA-MALAT1 in myocardial tissue was reduced,and HMGB1 and TLR4 protein content was reduced(P＜0.05).Conclusion Post-ischemic treatment can reduce the degree of myocardial ischemia-reperfusion injury in rats,and the mechanism may be related to the inhibition of lncRNA-MALAT1 and the regulation of downstream expression of HMGB1,TLR4 and IL-6.
关键词
缺血后处理/心肌缺血-再灌注损伤/肺腺癌转录子1/HMGB1/TLR4Key words
post-ischemic management/myocardial ischemia-reperfusion injury/lung adenocarcinoma transcript 1/HMGB1/TLR4引用本文复制引用
基金项目
河南省科技攻关联合共建项目(LHGJ20210752)
出版年
2024
NETL
NSTL
万方数据