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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
Role of NLRP3/Caspase-1/IL-1β inflammasome pathway in formation of aortic dissection in mice
- 陆军军医大学学报 2024年46卷第7期 页码：705-714
- 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：
[魏蜀亮，E-mail：shuliang_wei@163.com WEI Shuliang, E-mail: shuliang_wei@163.com
- 基金信息：四川省南充市科技局合作科研项目(22SXQT0007);川北医学院附属医院科研项目(2022LC018)
DOI：10.16016/j.2097-0927.202306105
中图分类号： R363.21;R392.13;R543.16收稿：2023-06-27，
修回：2023-10-03，
纸质出版：2024-04-15
- 稿件说明：
移动端阅览
向军, 何玲, 许宏志, 等. 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[J]. 陆军军医大学学报, 2024,46(7):705-714.
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.
向军, 何玲, 许宏志, 等. 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[J]. 陆军军医大学学报, 2024,46(7):705-714. DOI： 10.16016/j.2097-0927.202306105.
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
2
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
2
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(
n
=10，无干预)、β-氨基丙腈(β-aminopropionitrile，BAPN)组[
n
=20，饮水中加入1 g/(kg·d) BAPN
]
、BAPN+ MCC950组[
n
=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
2
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(
P
<
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%
vs
35%，
P
=0.004)，夹层相关病死率下降(35%
vs
15%，
P
=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(
P
<
0.05)。
结论
2
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
2
To investigate the role and mechanism of NLRP3/Caspase-1/IL-1β inflammasome pathway in the formation of aortic dissection in mice.
Methods
2
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
2
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 (
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
2
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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