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Effects of MCC950 on cognitive function in a mouse model of sepsis-associated encephalopathy / 中华急诊医学杂志
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-751863
Biblioteca responsável: WPRO
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 groupsthe 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.

Texto completo: Disponível Base de dados: WPRIM (Pacífico Ocidental) Idioma: Chinês Revista: Chinese Journal of Emergency Medicine Ano de publicação: 2019 Tipo de documento: Artigo
Texto completo: Disponível Base de dados: WPRIM (Pacífico Ocidental) Idioma: Chinês Revista: Chinese Journal of Emergency Medicine Ano de publicação: 2019 Tipo de documento: Artigo
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