MCC950对脓毒症相关脑病小鼠认知功能的影响

Q4 Nursing

中华急诊医学杂志 Pub Date : 2019-07-10 DOI:10.3760/CMA.J.ISSN.1671-0282.2019.07.010

Jingyu Zhang, Yunxia Fan, Qun Fu, Jing Wu, Zhi-qiang Zhou, Guo-min Li

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引用次数: 1

摘要

目的探讨Nod样受体蛋白3抑制剂MCC950对脓毒症相关性脑病（SAE）小鼠认知功能的影响。方法将90只成年雄性C57BL/6小鼠随机分为三组：假手术+生理盐水组（n=20，假手术组）、CLP+生理盐水（n=35，CLP组）和CLP+MCC950组（n=35、MCC950组）。通过盲肠结扎和穿刺（CLP）手术建立SAE小鼠模型。根据分组，在手术前30分钟和手术后第1、2、4和6天腹膜内注射盐水（10mL/kg）或MCC950（10mg/kg）。手术后7天，每组取6只小鼠。免疫印迹法检测海马NLRP3、凋亡相关斑点样蛋白（ASC）、白细胞介素-1β（IL-1β）和IL-18的含量。免疫组化法检测CA1区NLRP3阳性细胞数。每组中剩余的小鼠在手术后14天用于开放场地和恐惧条件测试。组间比较采用单向方差分析，成对比较采用SNK-q检验。P值<0.05被认为具有统计学意义。结果MCC950组与CLP组相比，上下文测试的冷冻时间显著增加[（137±21）s vs（84±15）s，P=0.013]，海马NLRP3、IL-1β和IL-18含量显著降低（P<0.05），这可能是由于NLRP3炎症小体和下游炎性细胞因子IL-1β和IL-18的抑制。关键词：脓毒症相关性脑病；认知功能；神经炎症；NLRP3炎症小体；白细胞介素-1β；白细胞介素-18

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Effects of MCC950 on cognitive function in a mouse model of sepsis-associated encephalopathy

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 speck-like protein (ASC), interleukin-1β (IL-1β) and IL-18. The number of NLRP3-positive cells in CA1 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 0.05). 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. Key words: Sepsis-associated encephalopathy; Cognitive function; Neuroinflammation; NLRP3 inflammasome; Interleukin-1β; Interleukin-18

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来源期刊

中华急诊医学杂志 Nursing-Emergency Nursing

CiteScore

0.10

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0.00%

发文量

8629

期刊介绍： Chinese Journal of Emergency Medicine is the only national journal which represents the development of emergency medicine in China. The journal is supervised by China Association of Science and Technology, sponsored by Chinese Medical Association, and co-sponsored by Zhejiang University. The journal publishes original research articles dealing with all aspects of clinical practice and research in emergency medicine. The columns include Pre-Hospital Rescue, Emergency Care, Trauma, Resuscitation, Poisoning, Disaster Medicine, Continuing Education, etc. It has a wide coverage in China, and builds up communication with Hong Kong, Macao, Taiwan and international emergency medicine circles.