Role of NLRP3/Caspase-1/IL-1β inflammasome pathway in formation of aortic dissection in mice

Jun XIANG; Ling HE; Hongzhi XU; Weiwei LIANG; Tailuan PENG; Shuliang WEI

doi:10.16016/j.2097-0927.202306105

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Role of NLRP3/Caspase-1/IL-1β inflammasome pathway in formation of aortic dissection in mice

Basic Medicine | 更新时间：2026-01-09

- Role of NLRP3/Caspase-1/IL-1β inflammasome pathway in formation of aortic dissection in mice
- Journal of Army Medical University Vol. 46, Issue 7, Pages: 705-714(2024)
- 作者机构：
  
  1.637000 四川南充，川北医学院附属医院心脏大血管外科
  2.637000 四川南充，川北医学院附属医院儿科/新生儿科
  3.637000 四川南充，川北医学院附属医院手术中心
- 作者简介：
- 基金信息：
  
  the Cooperative Scientific Research Project of Science and Technology Bureau of Nanchong in Sichuan Province(22SXQT0007);the Scientific Research Project of Affiliated Hospital of North Sichuan Medical College(2022LC018)
- DOI：10.16016/j.2097-0927.202306105
  CLC： R363.21;R392.13;R543.16
- Received：27 June 2023，
  
  Revised：2023-10-03，
  
  Published：15 April 2024
- 稿件说明：
移动端阅览
Jun XIANG, Ling HE, Hongzhi XU, et al. Role of NLRP3/Caspase-1/IL-1β inflammasome pathway in formation of aortic dissection in mice[J]. Journal of Army Medical University, 2024, 46(7): 705-714.
DOI：

Jun XIANG, Ling HE, Hongzhi XU, et al. Role of NLRP3/Caspase-1/IL-1β inflammasome pathway in formation of aortic dissection in mice[J]. Journal of Army Medical University, 2024, 46(7): 705-714. DOI： 10.16016/j.2097-0927.202306105.

摘要

目的

探讨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及机制。

方法

50只3周龄雄性C57BL/6小鼠(体质量10~13 g)按随机抽样法分为对照组(

=10，无干预)、β-氨基丙腈(β-aminopropionitrile，BAPN)组[

=20，饮水中加入1 g/(kg·d) BAPN

]

、BAPN+ MCC950组[

=20，饮水中加入1 g/(kg·d) BAPN、腹腔注射NLRP3抑制剂MCC950 20 mg/(kg·d)

]

。记录各组小鼠饮水量、体质量、主动脉夹层发生率、夹层相关病死率。采用HE染色观察主动脉壁炎症浸润；弹力纤维(elastic Van Gieson，EVG)染色观察主动脉壁弹力纤维断裂。采用免疫荧光检测NLRP3、IL-1β、α-SMA、OPN的平均荧光强度。采用Western blot检测NLRP3、Caspase-1、ASC、IL-1β、α-SMA、OPN表达水平。

结果

对照组无主动脉夹层发生及死亡，BAPN组主动脉夹层发生率为80%，夹层相关病死率为35%，且主动脉血管壁弹力纤维断裂、明显炎症浸润。与对照组比较，BAPN组中NLRP3、Caspase-1、ASC、IL-1β蛋白表达增加，收缩型蛋白α-SMA减少而合成型蛋白OPN增加(

0.05)。而给予NLRP3特异性抑制剂MCC950后，主动脉夹层发生率下降(80%

35%，

=0.004)，夹层相关病死率下降(35%

15%，

=0.144)，血管壁弹力纤维断裂、炎症浸润减少；与BAPN组比较，BAPN+ MCC950组NLRP3、Caspase-1、ASC、IL-1β蛋白表达降低，收缩型蛋白α-SMA表达增加而合成型蛋白OPN表达降低(

0.05)。

结论

小鼠主动脉夹层的发生与NLRP3/Caspase-1/IL-1β炎症小体通路活化有关，而NLRP3抑制剂MCC950能减少主动脉夹层发生，具有血管保护作用。

Abstract

Objective

To investigate the role and mechanism of NLRP3/Caspase-1/IL-1β 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 (

=10

normal diet)

β-aminopropionitrile (BAPN) group [

=20

drink water containing 1 g/(kg·d) BAPN

]

and BAPN+ MCC950 group [

=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-1β

decreased contractile α-SMA and increased synthetic protein OPN when compared with the control group (

0.05). While MCC950 treatment decreased the incidence of aortic dissection (80%

35%

=0.004) and aortic dissection-related mortality (35%

15%

=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 (

0.05).

Conclusion

The occurrence of aortic dissection in mice is associated with activation of NLRP3/Caspase-1/IL-1β inflammasome pathway. NLRP3 inhibitor

MCC950

can reduce the occurrence of aortic dissection and show a protective effect on blood vessels.

关键词

Keywords

references

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