Mechanism of Gegen Qinliantang against Vulnerable Plaque of Atherosclerosis: Based on Macrophage Pyroptosis Mediated by NF-κB/NLRP3/Caspase-1 Pathway
10.13422/j.cnki.syfjx.20220611
- VernacularTitle:基于NF-κB/NLRP3/Caspase-1通路介导的巨噬细胞焦亡探究葛根芩连汤对动脉粥样硬化易损斑块的干预机制
- Author:
Yi ZHENG
1
;
He GUO
1
;
Yong-rui BAO
1
;
Shuai WANG
1
;
Tian-jiao LI
1
;
Xi LUO
1
;
Huan ZHANG
1
;
Fei NI
1
;
Ying-zhu DUAN
1
;
Ying ZHANG
1
;
Rui YU
1
;
Xian-sheng MENG
1
Author Information
1. Liaoning University of Traditional Chinese Medicine,Shenyang 110847,China
- Publication Type:Journal Article
- Keywords:
Gegen Qinliantang;
atherosclerosis;
macrophages;
pyroptosis;
mechanism
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2022;28(11):70-78
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore the effect of Gegen Qinliantang (GQL) on vulnerable plaque of atherosclerosis based on the macrophage pyroptosis mediated by nuclear factor (NF)-κB/NOD-like receptor protein 3 (NLRP3)/cysteine-aspartic acid protease (Caspase)-1 pathway. MethodA total of 12 normal C57BL/6CNC mice were used as the control group, and 60 ApoE-/- mice of the same line were randomized into 5 groups: model group, low-dose, medium-dose, and high-dose GQL groups (GQL-D, GQL-Z, GQL-G groups, respectively), and western medicine group. The control group and model group were given (ig) equal volume sterile distilled, and GQL-D, GQL-Z, GQL-G and western medicine groups received (ig) corresponding concentration of drugs for 8 weeks. Aortic plaques were observed based on hematoxylin and eosin (HE) staining. Serum levels of interleukin (IL)-1β and IL-18 were detected by enzyme-linked immunosorbent assay (ELISA), protein levels of macrophage mannose receptor (CD206)/apoptosis-associated speck-like protein containing a CARD (ASC) and CD206/NLRP3 by double-labeling immunofluorescence, and C-terminal gasdermin D (GSDMD), N-terminal GSDMD, NLRP3, pro-cysteinyl aspartate specific proteinase 1 (pro-Caspase-1) and NF-κB p65 by Western blot. ResultCompared with the control group, model group demonstrated serious pathological changes, rise of the levels of serum IL-1β and IL-18 and tissue ASC, NLRP3, C-terminal GSDMD, N-terminal GSDMD, pro-Caspase-1, and NF-κB p65, and decrease of CD206 level (P<0.05). As compared with model group, the administration groups showed alleviation of the lesions in aortic wall, decrease in levels of serum IL-1β and IL-18 and tissue ASC, NLRP3, C-terminal GSDMD, N-terminal GSDMD, pro-Caspase-1, and NF-κB p65, and rise of CD206 level, with significant difference between some groups (P<0.05). ConclusionGegen Qinliantang alleviates vulnerable plaque of atherosclerosis by regulating NF-κB/NLRP3/Caspase-1 pathway and further relieving macrophage pyroptosis.