Effects of aspirin on myocardial injury in rats with myocardial ischemia/reperfusion by regulating miR-340-5p/HMGB1/TLR4 pathway

CHEN Xinghua; ZHANG Jizhuo; HAN Lu

doi:10.6039/j.issn.1001-0408.2022.20.15

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Effects of aspirin on myocardial injury in rats with myocardial ischemia/reperfusion by regulating miR-340-5p/HMGB1/TLR4 pathway

更新时间：2025-12-05

- Effects of aspirin on myocardial injury in rats with myocardial ischemia/reperfusion by regulating miR-340-5p/HMGB1/TLR4 pathway
- ZHONGGUO YAOFANG Vol. 33, Issue 20, Pages: 2508-2513(2022)
- 作者机构：
  
  1.首都医科大学附属北京世纪坛医院心脏外科，北京　100038
  2.首都医科大学附属北京朝阳医院医学研究中心，北京　100020
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2022.20.15
  CLC： R965
- Received：31 March 2022，
  
  Revised：2022-08-15，
  
  Published：30 October 2022
- 稿件说明：
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陈兴华,张继倬,韩露.阿司匹林调节miR-340-5p/HMGB1/TLR4通路对大鼠心肌缺血/再灌注损伤的影响[J].中国药房,2022,33(20):2508-2513.

CHEN Xinghua,ZHANG Jizhuo,HAN Lu.Effects of aspirin on myocardial injury in rats with myocardial ischemia/reperfusion by regulating miR-340-5p/HMGB1/TLR4 pathway[J].ZHONGGUO YAOFANG,2022,33(20):2508-2513.
陈兴华,张继倬,韩露.阿司匹林调节miR-340-5p/HMGB1/TLR4通路对大鼠心肌缺血/再灌注损伤的影响[J].中国药房,2022,33(20):2508-2513. DOI： 10.6039/j.issn.1001-0408.2022.20.15.

CHEN Xinghua,ZHANG Jizhuo,HAN Lu.Effects of aspirin on myocardial injury in rats with myocardial ischemia/reperfusion by regulating miR-340-5p/HMGB1/TLR4 pathway[J].ZHONGGUO YAOFANG,2022,33(20):2508-2513. DOI： 10.6039/j.issn.1001-0408.2022.20.15.

摘要

目的

探讨阿司匹林（Asp）通过调节微RNA-340-5p（miR-340-5p）/高迁移率族蛋白1（HMGB1）/Toll样受体4（TLR4）通路对大鼠心肌缺血/再灌注（I/R）损伤的影响。

方法

将雄性SD大鼠分为假手术（Sham）组（开胸不结扎）、I/R组（构建I/R损伤模型）、Asp预处理（I/R+Asp）组（Asp预处理7 d+造模）、I/R+Asp+in-miR-340-5p组[Asp预处理7 d+提前转染miR-340-5p抑制物+造模]和I/R+Asp+HMGB1组（Asp预处理7 d+提前转染过表达HMGB1+造模），每组20只。检测各组大鼠心肌损伤指标（乳酸脱氢酶、肌酸激酶同工酶MB、心肌肌钙蛋白Ⅰ）、炎症和氧化应激指标（髓过氧化物酶、超氧化物歧化酶、谷胱甘肽过氧化物酶、丙二醛）水平，观察其心肌组织病理改变，检测其心肌梗死面积、细胞凋亡情况以及心肌组织中miR-540-5p和HMGB1、TLR4蛋白的表达情况；以大鼠心肌细胞H9C2为对象，考察miR-340-5p与HMGB1的靶向关系。

结果

Asp预处理可显著抑制I/R损伤模型大鼠血清心肌损伤指标水平的升高，可减轻炎症反应、抑制氧化应激反应、缩小心肌梗死面积并减少细胞凋亡，可显著上调miR-340-5p的表达并下调HMGB1、TLR4蛋白的表达（

＜0.05）；抑制miR-340-5p或过表达HMGB1均可逆转Asp的上述保护作用（

＜0.05）。细胞实验结果显示，miR-340-5p可靶向负调控HMGB1的表达（

＜0.05）。

结论

Asp可通过调节miR-340-5p/HMGB1/TLR4通路来减轻大鼠炎症反应和氧化应激，减少心肌组织中的细胞凋亡，进而发挥对心肌I/R损伤的保护作用。

Abstract

OBJECTIVE

To investigate the effects of aspirin （Asp） on myocardial ischemia/reperfusion （I/R） injury by regulating microRNA-340-5p （miR-340-5p）/high mobility group box 1 （HMGB1）/Toll-like receptor 4 （TLR4） pathway.

METHODS

Male SD rats were divided into sham operation （Sham） group （thoracotomy without ligation）， I/R group （I/R injury model was constructed）， and Asp pretreatment （I/R+Asp） group （7 d of Asp pretreatment+modeling）， I/R+Asp+in-miR-340-5p group [Asp pretreatment 7 d+transfection with miR-340-5p inhibitor 48 h before modeling+modeling] and I/R+Asp+HMGB1 group （7 d of Asp pretreatment+transfection with overexpression of HMGB1 48 h before modeling+modeling）， with 20 rats in each group. The levels of myocardial injury indexes [lactate dehydrogenase， creatine kinase isoenzyme-MB， cardiac troponin Ⅰ]， inflammation and oxidative stress indexes [myeloperoxidase， superoxide dismutase， glutathione peroxidase， malondialdehyde] were detected in each group， and the pathological changes of myocardial tissue were observed. The myocardial infarction area， cell apoptosis and the expression of miR-540-5p， HMGB1 and TLR4 in myocardial tissue were detected. Cardiomyocyte H9C2 of rats was used as the object to investigate the targeting relationship between miR-340-5p and HMGB1.

RESULTS

Asp pretreatment could significantly inhibit the increase of serum myocardial injury indexes in I/R model rats， reduce inflammation and inhibit oxidative stress， reduce myocardial infarct size and apoptosis， and significantly up-regulated the expression of miR-340-5p and down-regulated the expression of HMGB1 and TLR4 proteins （

＜0.05）； inhibition of miR-340-5p or overexpression of HMGB1 could reverse the above protective effects of Asp （

＜0.05）. miR-340-5p could target and negatively regulate HMGB1 expression （

＜0.05）.

CONCLUSIONS

Asp can reduce inflammation and oxidative stress by regulating the miR-340-5p/HMGB1/TLR4 pathway， reduce apoptosis in myocardial tissue， and play a protective role against myocardial I/R injury.

关键词

Keywords

references

DRAGASEVIC N ， JAKOVLJEVIC V ， ZIVKOVIC V ， et al . The role of aldosterone inhibitors in cardiac ischemia-reperfusion injury [J ] . Can J Physiol Pharmacol ， 2021 ， 99 （ 1 ）： 18 - 29 .

WANG W J ， WANG B L ， SUN S K ， et al . Inhibition of adenosine kinase attenuates myocardial ischaemia/reper-fusion injury [J ] . J Cell Mol Med ， 2021 ， 25 （ 6 ）： 2931 - 2943 .

BAI Q J ， LI Y ， SONG K P ， et al . Knockdown of XIST up-regulates 263294miR-340-5p to relieve myocardial ischae-mia-reperfusion injury via inhibiting cyclin D1 [J ] . ESC Heart Fail ， 2022 ， 9 （ 2 ）： 1050 - 1060 .

GAO Y Z ， WANG L M ， NIU Z Q ， et al . miR-340-5p inhibits pancreatic acinar cell inflammation and apoptosis via targeted inhibition of HMGB1 [J ] . Exp Ther Med ， 2022 ， 23 （ 2 ）： 140 .

CHEN C B ， LU C H ， HE D W ， et al . Inhibition of HMGB1 alleviates myocardial ischemia/reperfusion injury in diabetic mice via suppressing autophagy [J ] . Microvasc Res ， 2021 ， 138 ： 104204 .

DINGH S ， YANG J ， YANG J ， et al . Fluvastatin attenuated ischemia/reperfusion-induced autophagy and apoptosis in cardiomyocytes through down-regulation HMGB1/TLR4 signaling pathway [J ] . Mol Biol Rep ， 2021 ， 48 （ 5 ）： 3893 - 3901 .

吴咏梅 . 疏血通与阿司匹林合用对大鼠脑缺血/再灌注损伤的药效学研究 [D ] . 长春：长春中医药大学， 2018 .

WU X L ， WEI M H ， ZHANG H F ， et al . The protective effect of aspirin against myocardial hypertrophy in rats [J ] . Biomed Res Int ， 2021 ， 2021 ： 2043415 .

WU Z J ， LI X W ， LI X Y ， et al . Effects of aspirin on myocardial ischemia-reperfusion injury in rats through STAT3 signaling pathway [J ] . Biomed Res Int ， 2021 ， 2021 ： 9931885 .

YANG J ， YANG C J ， YANG J ， et al . RP105 alleviates myocardial ischemia reperfusion injury via inhibiting TLR4/TRIF signaling pathways [J ] . Int J Mol Med ， 2018 ， 41 （ 6 ）： 3287 - 3295 .

MCCORMICK-ELL J ， CONNELL N . Laboratory safety，biosecurity，and responsible animal use [J ] . ILAR J ， 2019 ， 60 （ 1 ）： 24 - 33 .

WENZ J ， XIN H ， WANGY C ， et al . Emerging roles of circRNAs in the pathological process of myocardial in-farction [J ] . Mol Ther Nucleic Acids ， 2021 ， 26 ： 828 - 848 .

WIJNTJENSG W ， FENGLER K ， FUERNAU G ， et al . Prognostic implications of microcirculatory perfusion versus macrocirculatory perfusion in cardiogenic shock：a CULPRIT-SHOCK substudy [J ] . Eur Heart J Acute Cardiovasc Care ， 2020 ， 9 （ 2 ）： 108 - 119 .

HAUSENLOYD J ， SCHULZ R ， GIRAO H ， et al . Mitochondrial ion channels as targets for cardioprotection [J ] . J Cell Mol Med ， 2020 ， 24 （ 13 ）： 7102 - 7114 .

ANDREADOU I ， SCHULZ R ， PAPAPETROPOULOS A ， et al . The role of mitochondrial reactive oxygen species，NO and H 2 S in ischaemia/reperfusion injury and car-dioprotection [J ] . J Cell Mol Med ， 2020 ， 24 （ 12 ）： 6510 - 6522 .

HUANG Z ， XU Y S ， WAN M P ， et al . miR-340：a multifunctional role in human malignant diseases [J ] . Int J Biol Sci ， 2021 ， 17 （ 1 ）： 236 - 246 .

ZHU Y H ， YANG X W ， ZHOU J ， et al . miR-340-5p me-diates cardiomyocyte oxidative stress in diabetes-induced cardiac dysfunction by targeting Mcl-1 [J ] . Oxid Med Cell Longev ， 2022 ， 2022 ： 3182931 .

YANG M L ， WOOLFENDENH C ， ZHANG Y Y ， et al . Intact RNA structurome reveals mRNA structure-mediated regulation of miRNA cleavage in vivo [J ] . Nucleic Acids Res ， 2020 ， 48 （ 15 ）： 8767 - 8781 .

YANG H ， WANG H C ， ANDERSSON U . Targeting inflammation driven by HMGB1 [J ] . Front Immunol ， 2020 ， 11 ： 484 .

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