Itaconic acid improves vascular endothelial dysfunction in diabetic mice by inhibiting endothelial cell apoptosis
10.13406/j.cnki.cyxb.003756
- VernacularTitle:衣康酸通过抑制内皮细胞凋亡改善糖尿病小鼠血管内皮功能障碍
- Author:
Jia TANG
1
;
Yuehui YIN
;
Yunlin CHEN
;
Jian YANG
;
Fuwei ZHANG
;
Luning WANG
Author Information
1. 重庆医科大学第二附属医院心血管内科/重庆市心律失常重点实验室,重庆 401336
- Keywords:
itaconic acid;
diabetes;
endothelial dysfunction;
cell apoptosis
- From:
Journal of Chongqing Medical University
2025;50(9):1195-1201
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the protective effect and mechanism of 4-octyl itaconate(4-OI)on vascular endothelial function in diabetic mice,since endothelial dysfunction is the key and initial factor for vascular complications in diabetes.Methods:The db/db mice were used to establish a mouse model of diabetes,and high glucose(HG)-induced human umbilical vein endothelial cells(HUVECs)were used to establish a cell model of diabetes.After 4-OI treatment,HE staining,Masson staining,and reticular fiber staining were used to observe pathological changes of the thoracic aorta in the control group,the model group,and the intervention group;Western blot was used to measure the expression of α-smooth muscle actin(α-SMA),a marker for endothelial fibrosis;immuno-fluorescence assay was used to measure the expression levels of Bcl-2-associated X protein(BAX)and B-cell lymphoma-2(Bcl-2)in the thoracic aorta of mice in the control group,the model group,and the intervention group;immunoblotting was used to observe the effect of 4-OI intervention on the expression of BAX,Bcl-2,and the proteins associated with the cytochrome C(CytC)/cysteinyl aspartate specific proteinase(caspase)pathway in HG-induced HUVECs.Results:The results showed that 4-OI could significantly improve vascular endothelial dysfunction in db/db diabetic mice.Compared with the model group,the intervention group had a significant increase in the expression of Bcl-2(0.73±0.07 vs.0.52±0.04,F=49.380,P=0.009)and a significant reduction in the expression of BAX(1.41±0.14 vs.1.89±0.12,F=37.270,P=0.008)after 4-OI treatment.In the cell model of HUVECs induced by HG,compared with the high glucose group,the intervention group had a sig-nificant increase in the expression of Bcl-2(1.22±0.04 vs.0.81±0.09,F=75.410,P<0.001)and a significant reduction in the expres-sion of BAX(0.83±0.04 vs.1.12±0.04,F=268.100,P<0.001)after 4-OI treatment,as well as significant reductions in the expres-sion of CytC(0.61±0.03 vs.1.01±0.03,F=234.000,P<0.001),caspase-9(0.62±0.03 vs.1.04±0.04,F=164.300,P<0.001),and caspase-3(0.92±0.06 vs.1.74±0.04,F=424.100,P<0.001).Conclusion:In conclusion,4-OI inhibits vascular endothelial cell apoptosis in diabetic mice by affecting the expression of the CytC/Caspase pathway factors,thereby improving vascular endothelial dys-function in diabetes.
