Page 86 - 《中国药房》2022年20期

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

陈兴华 ，张继倬 ，韩 露（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
1＊
1 #
2
附属北京朝阳医院医学研究中心，北京 100020）
中图分类号 R965 文献标志码 A 文章编号 1001-0408（2022）20-2508-06
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（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。
关键词 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

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（1. Dept. of Cardiac Surgery，Beijing Shijitan Hospital Affiliated to
1
2
1
Capital Medical University，Beijing 100038，China；2. Medical Research Center，Beijing Chaoyang Hospital
Affiliated to Capital Medical University，Beijing 100020，China）

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（P＜0.05）；inhibition of miR-340-5p or overexpression of HMGB1
could reverse the above protective effects of Asp（P＜0.05）. miR-340-5p could target and negatively regulate HMGB1 expression
（P＜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.
KEYWORDS aspirin； microRNA-340-5p； high mobility
＊第一作者 主治医师，硕士。研究方向：心肌缺血/再灌注损伤。
E-mail：sjtxzwk@163.com group box 1； Toll-like receptor 4； myocardial ischemia/
reperfusion；myocardial injury；rats
# 通信作者 主任医师，硕士。研究方向：心肌缺血/再灌注损伤。
E-mail：13911028861@163.com

·2508· China Pharmacy 2022 Vol. 33 No. 20 中国药房 2022年第33卷第20期