Effects of aspirin on myocardial injury in rats with myocardial ischemia/reperfusion by regulating miR-340-5p/HMGB1/TLR4 pathway
- VernacularTitle: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
- Author:
Xinghua CHEN
1
;
Jizhuo ZHANG
1
;
Lu HAN
2
Author Information
1. Dept. of Cardiac Surgery，Beijing Shijitan Hospital Affiliated to Capital Medical University，Beijing 100038，China
2. Medical Research Center，Beijing Chaoyang Hospital Affiliated to Capital Medical University，Beijing 100020，China
- Publication Type:Journal Article
- Keywords:
aspirin;
microRNA-340-5p;
high mobility
- From:
China Pharmacy
2022;33(20):2508-2513
- CountryChina
- Language:Chinese
-
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 .
