Levosimendan alleviates coronary microembolization-induced myocardial injury through LOX-1/p38 MAPK pathway
10.3760/cma.j.issn.1671-0282.2021.09.002
- VernacularTitle:左西孟旦调控LOX-1/p38 MAPK通路减轻冠状动脉微栓塞后心肌损伤
- Author:
You ZHOU
1
;
Jiangyou WANG
;
Tao LIU
;
Yangchun LIU
;
Huafeng YANG
;
Lang LI
Author Information
1. 广西医科大学第一附属医院心血管内科，南宁 530021
- Keywords:
Coronary microembolization;
Levosimendan;
LOX-1;
p38 MAPK;
Cardiomyocyte apoptosis
- From:
Chinese Journal of Emergency Medicine
2021;30(9):1051-1057
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To study the effect of levosimendan on coronary microembolization (CME)-induced myocardial injury and LOX-1/p38MAPK pathway.Methods:Microspheres were injected into coronary anterior descending branch to construct swine CME model, swine was given levosimendan by continuous intravenous drip for 24 h before modeling, and myocardial-specific overexpression of lectin-like oxidized low density lipoprotein receptor 1 (LOX-1) was achieved through coronary artery injection of adeno-associated virus (AAVs) at 2 weeks before modeling. Then, echocardiography was used to measure cardiac function; HE staining and HBFP staining were used to observe the pathological changes of myocardium and myocardial microinfarction area, respectively; ELISA was used to detect the serum level of cTnI; TUNLE staining was used to detect cardiomyocyte apoptotic index; the LOX-1, Bax, caspase-3 p12, Bcl-2, and p-p38 MAPK protein in myocardial tissue was observed by immunofluorescence method.Results:Compared to the sham group, the LVEF, LVFS, and CO value in the CME group were decreased, while the LVEDd value was increased significantly (all P<0.05); the area of myocardial micro-infarction, serum cTnI level and cardiomyocyte apoptotic rate in the CME group were increased significantly (all P<0.05); the protein levels of Bax, caspase-3 p12, LOX-1, and p-p38 MAPK were increased significantly, while the Bcl-2 level was decreased significantly ( P<0.05). Levosimendan pretreatment significantly improved cardiac dysfunction, reduced the area of myocardial micro-infarction and serum cTnI level, alleviated cardiomyocyte apoptosis, and significantly reduced the LOX-1 and p-p38 MAPK protein expression levels following CME (all P<0.05); while pretreatment with levosimendan and LOX-1 overexpression AAVs simultaneously abolished the effects of pretreatment with levosimendan alone (all P<0.05). Conclusion:Levosimendan alleviates CME-induced myocardial injury through inhibiting cardiomyocyte apoptosis mediated by LOX-1/p38 MAPK signaling pathway.
