Model evaluation and mechanism investigation of chronic stress aggra-vating myocardial injury in mice with atherosclerosis
10.3969/j.issn.1000-4718.2024.09.009
- VernacularTitle:慢性应激加重动脉粥样硬化小鼠心肌损伤的模型评价及机制研究
- Author:
Ping NI
1
;
Sitong LIU
;
Ruige SUN
;
Haijun MA
;
Hong SUN
;
Huan ZHANG
;
Jian LIANG
;
Chengyu DU
;
You YU
;
Rui YU
Author Information
1. 辽宁中医药大学,辽宁 沈阳 110847
- Keywords:
atherosclerotic;
chronic stress;
myocardial injury;
mitochondria;
mitochondrial allostatic load
- From:
Chinese Journal of Pathophysiology
2024;40(9):1635-1644
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To investigate the mechanism of chronic stress-induced myocardial injury in atherosclerotic(AS)mice.METHODS:Eight-week-old SPF-grade male ApoE-/-mice and C57BL/6J mice used in this study.The mice received dietary intervention for 10 weeks followed by pathological examination to test the successful AS modeling.After AS establishment,the mice were exposed to chronic unpredictable mild stress(CUMS)for 6 weeks and then divided into five groups:control,CUMS,AS-regular diet(AS-r)+CUMS,AS-high-fat diet(AS-h),and AS-h+CUMS.During CUMS,open-field test and sucrose preference test were performed on mice in all groups.Blood lipids were characterized using an automatic biochemical analyzer.Hematoxylin-eosin(HE)and oil red O staining were performed to evaluate pathological changes in the aortic root.Cardiac function was assessed using echocardiography.The serum concentration of myocardial injury markers and ATP content was detected by ELISA.Transmission electron microscopy was employed to observe the ul-trastructure of myocardial mitochondria.Myocardial mitochondrial oxygen consumption rate was determined using the Oxy-graph-2k high-resolution respiratory energy metabolism analyzer.Western blot was conducted to quantify the expression of B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),and cleaved caspase-3.RESULTS:compared with the Control group,the total distance traveled,the number of entries into the central area,and the sucrose preference rate were significantly decreased in all CUMS groups(P<0.05).All AS groups exhibited varying levels of lipid deposition and endo-thelial damage in the aortic root,along with a significant reduction in cardiac function(P<0.05)and varying degrees of myocardial injury(P<0.05).In the AS-h+CUMS and AS-r+CUMS groups,myocardial mitochondrial structure was signifi-cantly disrupted.ATP content was significantly reduced(P<0.05),and the rates of oxygen consumption associated with mitochondrial respiratory chain complex I,mitochondrial respiratory chain complexes I+II,and the maximum respiratory capacity of the electron transport system were all significantly decreased(P<0.05).Moreover,the protein levels of Bax and cleaved caspase-3 were significantly increased(P<0.05),while that of Bcl-2 protein was significantly decreased(P<0.05).CONCLUSION:Chronic stress triggers mitochondrial non-steady-state load by disrupting myocardial structure and energy metabolism in AS mice,promoting myocardial cell apoptosis and myocardial injury.
