Effect of nuclear transcription factor kappa B/NOD-like receptor family pyrin domain containing protein 3 pathway on lipid deposition and autophagy related protein expressions in aortic atherosclerosis mice
10.3760/cma.j.cn115354-20220324-00165
- VernacularTitle:NF-κB/NLRP3通路对动脉粥样硬化小鼠脂质沉积及自噬相关蛋白表达的影响
- Author:
Kangning ZHU
1
;
Fengxia GUO
;
Lan GAO
Author Information
1. 河南省人民医院检验科,郑州 450003
- Keywords:
Atherosclerosis;
Nuclear transcription factor kappa B;
NOD-like receptor family pyrin domain containing protein 3;
Autophagy;
Lipid deposition
- From:
Chinese Journal of Neuromedicine
2022;21(6):580-586
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effect of nuclear transcription factor kappa B (NF-κB)/NOD-like receptor family pyrin domain containing protein 3 (NLRP3) pathway on lipid deposition and autophagy related protein expressions in aortic atherosclerosis mice.Methods:Ten 6-week-old male C57BL/6 mice were used as control group, and 20 male apolipoprotein E gene knockout ( ApoE-/-) mice at the same age were randomly divided into AS group and bortezomib (BTZ) group ( n=10). Mice in the AS group and BTZ group were fed with high-fat diet for 8 weeks; and then, mice in the BTZ group were injected intraperitoneally with 50 μg/kg BTZ (twice a week, for 4 weeks), while mice in the AS group were injected with same amount of saline. The general states of mice in each group were observed during the experiment process. Twelve weeks after intervention, the body weight and the levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) were measured; the pathological morphology and lipid deposition of plaques at the aortic roots were observed by oil red O staining and HE staining; the expressions of NF-κB and NLRP3 were detected by immunohistochemistry; the expressions of Beclin-1, P62, and Atg12 were measured by Western blotting. Results:After 12 weeks of intervention, the body weight, contents of TC and LDL, pathological degrees, proportion of lipid deposition, positive expressions of NF-κB and NLRP3, and P62 protein expression in the AS group and BTZ group were significantly higher than those in the control group, while these indexes in the BTZ group were significantly lower than those in the AS group ( P<0.05); HDL content, protein expression levels of Beclin-1 and Atg12 in the AS group and BTZ group was significantly lower than that in the control group, while these indexes in the BTZ group were significantly higher than those in the AS group ( P<0.05). Conclusion:Inhibition of NF-κB/NLRP3 pathway can reduce lipid deposition by regulating lipid content and mediate the autophagy related protein expressions to promote autophagy, thereby inhibiting the process of AS.