Role of NLRP3/Caspase-1/IL-1β inflammasome pathway in formation of aortic dissection in mice
10.16016/j.2097-0927.202306105
- VernacularTitle:NLRP3/Caspase-1/IL-1β炎症小体通路在小鼠主动脉夹层形成中的作用
- Author:
Jun XIANG
1
;
Ling HE
;
Hongzhi XU
;
Weiwei LIANG
;
Tailuan PENG
;
Shuliang WEI
Author Information
1. 637000 四川 南充,川北医学院附属医院心脏大血管外科
- Keywords:
aortic dissection;
aortic aneurysm;
NLRP3;
signaling pathway
- From:
Journal of Army Medical University
2024;46(7):705-714
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the role and mechanism of NLRP3/Caspase-1/IL-1 β inflammasome pathway in the formation of aortic dissection in mice.Methods Fifty male C57BL/6 mice(3 weeks old,body weight 10～13 g)were divided into control group(n =10,normal diet),β-aminopropionitrile(BAPN)group[n =20,drink water containing 1 g/(kg·d)BAPN],and BAPN+MCC950 group[n=20,drink water containing 1 g/(kg·d)BAPN and intraperitoneal injection of 20 mg/(kg·d)NLRP3 inhibitor,MCC950]by random sampling.Water intake,body weight,incidence of aortic dissection and aortic dissection-related mortality were recorded.The inflammatory infiltration in the aorta was observed with HE staining,elastic fiber breakage was observed by elastic Van Gieson(EVG)staining,average fluorescence intensity of NLRP3,IL-1β,α-SMA and OPN was detected by immunofluorescence assay,and protein expression levels of NLRP3,Caspase-1,ASC,IL-1β,α-SMA and OPN were measured with Western blotting.Results No aortic dissection or death was observed in the control group.The BAPN group had an incidence of aortic dissection of 80％,aortic dissection-related mortality of 35％,and obvious broken elastic fibers and inflammatory infiltrate in the aortic wall,and increased expression levels of NLRP3,Caspase-1,ASC and IL-1 β,decreased contractile α-SMA and increased synthetic protein OPN when compared with the control group(P<0.05).While MCC950 treatment decreased the incidence of aortic dissection(80％vs 35％,P=0.004)and aortic dissection-related mortality(35％vs 15％,P=0.144),alleviated the broken elastic fibers and inflammatory infiltrate in the aortic wall,and down-regulated the expression of NLRP3,Caspase-1,ASC and IL-1β,enhanced contractile α-SMA and decreased the synthetic protein when compared with the BAPN group(P<0.05).Conclusion The occurrence of aortic dissection in mice is associated with activation of NLRP3/Caspase-1/IL-1 β inflammasome pathway.NLRP3 inhibitor,MCC950,can reduce the occurrence of aortic dissection and show a protective effect on blood vessels.
