Mechanism of inhibiting acetyl CoA carboxylase 2 to improve cardiac dysfunction in septic mice
10.16016/j.2097-0927.202406038
- VernacularTitle:抑制乙酰辅酶A羧化酶2改善脓毒症小鼠心功能障碍的机制研究
- Author:
Yunxia DU
1
;
Han SHE
;
Yinyu WU
;
Yi WANG
;
Yuanqun ZHOU
;
Weifei WANG
;
Tao LI
;
Yi HU
;
Qingxiang MAO
Author Information
1. 400042 重庆,陆军特色医学中心麻醉科;400042 重庆,陆军特色医学中心野战外科研究部战伤休克与输血研究室
- Keywords:
sepsis;
cardiomyocytes;
acetyl-CoA carboxylase 2;
calcium sensitivity;
malonyl CoA
- From:
Journal of Army Medical University
2024;46(24):2689-2697
- CountryChina
- Language:Chinese
-
Abstract:
Objective To observe the ameliorative effect of inhibiting acetyl-CoA carboxylase 2(ACC2)on cardiac dysfunction in septic mice and investigate its underlying mechanism.Methods Mouse model of sepsis was established by cecal ligation and perforation.A total of 24 male C57BL/6 mice(aged 8 weeks,weighing 20～25 g)were divided into sham operation group,sepsis group and ND-630+sepsis group.The cardiac specific ACC2 knockout(ACC2△CM)mice were constructed by Cre-LoxP recombinase system,and ACC2flox/flox Myh6-Cre-(ACC2fl/fl)mice were used as control.Several genetically engineered mice(8 weeks old,20～25 g,male)were divided into ACC2fl/fl+sham operation group,ACC2fl/fl+sepsis group,ACC2△CM+sepsis group,ACC2△CM+Mal-CoA+sepsis group,and ACC2△CM+sham operation group according to the random number table method.The contractile function and myofilament calcium sensitivity of cardiomyocytes were measured by a cell microtensiometer.Western blotting was used to detect the expression level of ACC2,and ELISA was employed to measure the level of malonyl-CoA(Mal-CoA)in myocardial tissue.The survival of the mice in 36 h after sepsis was observed.Results Compared with the sham operation group,the contraction amplitude of cardiomyocytes in sepsis group was decreased markedly,and the calcium sensitivity decreased significantly as well(P＜0.05).Based on the ACC2fl/fl+sham operation group,the ACC2△CM+sepsis group showed significant improvement in myocardial contraction compared with the ACC2fl/fl+sepsis group,with the contraction amplitude of cardiomyocytes recovered by 48.1％,and significantly restored calcium sensitivity(P＜0.05).ACC2△CM+Mal-CoA+sepsis group showed a notable decrease in myocardial cell contraction amplitude and a significant decrease in calcium sensitivity when compared to the ACC2△CM+sepsis group(P＜0.05).Compared with the sepsis group,the contraction amplitude of cardiomyocytes in the ND-630+sepsis group increased significantly,and the calcium sensitivity of myofilament also increased(P＜0.05).The expression level of ACC2 protein in the myocardial tissue of mice in the sepsis group increased compared to the sham operation group(P＜0.05).The level of myocardial Mal-CoA in the sepsis group was higher than that in the sham operation group(P＜0.05);Mal-CoA level in the myocardium of ACC2△CM+sepsis group mice was lower than that of sepsis group(P＜0.05).The 36-hour survival rate of the ACC2△CM+sepsis group.mice was 37.5％higher than that of the ACC2fl/fl+sepsis group mice.(P＜0.05).Conclusion Inhibition of ACC2 exerts a protective effect on myocardial contractility and calcium sensitivity in septic mice by reducing Mal-CoA.
