Effects of MCC950 on cognitive function in a mouse model of sepsis-associated encephalopathy
10.3760/cma.j.issn.1671-0282.2019.07.010
- VernacularTitle:MCC950对脓毒症相关性脑病小鼠认知功能的影响
- Author:
Jingyun ZHANG
1
;
Yunxia FAN
;
Qun FU
;
Jing WU
;
Zhiqiang ZHOU
;
Guomin LI
Author Information
1. 江苏大学附属金坛医院麻醉科
- Keywords:
Sepsis-associated encephalopathy;
Cognitive function;
Neuroinflammation;
NLRP3 inflammasome;
Interleukin-1β;
Interleukin-18
- From:
Chinese Journal of Emergency Medicine
2019;28(7):851-854
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effects of Nod-like receptor protein 3 inhibitor MCC950 on cognitive function in a mouse model of sepsis-associated encephalopathy (SAE).Methods Ninety adult male C57BL/6 mice were randomly (random number) divided into three groups:the sham + saline group (n=20,sham group),CLP + saline group (n=35,CLP group),and CLP + MCC950 group (n=35,MCC950 group).SAE mouse model was established by cecal ligation and puncture (CLP) surgery.Saline (10 mL/kg) or MCC950 (10 mg/kg) was intraperitoneally injected 30 min before surgery and on day 1,2,4 and 6 after surgery according the grouping.Seven days after surgery,six mice were taken from each group.Western blot was used to detect the hippocampal content of NLRP3,apoptosis-associated specklike protein (ASC),interleukin-1β (IL-1β) and IL-18.The number of NLRP3-positive cells in CA 1 region were detected by immunohistochemical analysis.The remaining mice in each group were used for open field and fear conditioning tests 14 days after surgery.One-way analysis of variance was used for inter-group comparison,and SNK-q test was used for pairwise comparison.A P value ＜0.05 was considered statistically significant.Results Compared the MCC950 group with the CLP group,the freezing time of context test was significantly increased [(137±21) s vs (84±15) s,P=0.013],the hippocampal content of NLRP3,IL-1β and IL-18 were significantly reduced (P＜0.01),and the number of NLRP3-immunoreactive cells per mm2 in CA region were significantly decreased (23±5 vs 74±13,P＜0.01).There was no significant changes in protein level of ASC and results of open field tests (P＞0.05).Conclusions MCC950 administration can improve cognitive function in a mouse model of SAE,which is probably due to the inhibition of NLRP3 inflammasome and downstream inflammatory cytokines IL-1β and IL-18.
