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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
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| 篇名： | 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 |
| TITLE： | Effects of aspirin on myocardial injury in rats with myocardial ischemia/reperfusion by regulating miR-340-5p/HMGB1/TLR4 pathway |
| 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7d+造模）、I/R+Asp+in-miR-340-5p组[Asp预处理7d+提前转染miR-340-5p抑制物+造模]和I/R+Asp+HMGB1组（Asp预处理7d+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（P＜0.05）；抑制miR-340-5p或过表达HMGB1均可逆转Asp的上述保护作用（P＜0.05）。细胞实验结果显示，miR-340-5p可靶向负调控HMGB1的表达（P＜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 a spirin （Asp） on myocardia l 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+HMGB 1 group （7 d of Asp pretreatment+transfection with overexpression of HMGB 1 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 TLR 4 in myocardial tissue were detected . Cardiomyocyte H 9C2 of rats was used as the object to investigate the targeting relationship between miR -340-5p and HMGB 1. 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 HMGB 1 and TLR 4 proteins（P＜0.05）；inhibition of miR -340-5p or overexpression of HMGB 1 could reverse the above protective effects of Asp （P＜0.05）. miR-340-5p could target and negatively regulate HMGB 1 expression （P＜0.05）. CONCLUSIONS Asp can reduce inflammation and oxidative stress by regulating the miR -340-5p/HMGB1/TLR4 pathway，reduce apoptosis i n myocardial tissue ，and play a protective role against myocard ial I/R injury . |
| 期刊： | 2022年第33卷第20期 |
| 作者： | 陈兴华，张继倬，韩露 |
| AUTHORS： | CHEN Xinghua，ZHANG Jizhuo，HAN Lu |
| 关键字： | 阿司匹林；微RNA-340-5p；高迁移率族蛋白1；Toll样受体4；心肌缺血/再灌注；心肌损伤；大鼠 |
| KEYWORDS： | aspirin； microRNA-340-5p； high mobility |
| 阅读数： | 184 次 |
| 本月下载数： | 5 次 |
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