七氟烷对衰老模型大鼠认知功能的影响及机制初探  

Effect of sevoflurane on cognitive function in aging model rats and its mechanism

作　　者：周骏洁 张超 杨鑫鑫 方旭 朱昭琼 Zhou Jun-jie;Zhang Chao;Yang Xin-xin;Fang Xu;Zhu Zhao-qiong(Department of Anesthesiology,Affiliated Hospital of Zunyi Medical University,Zunyi 563300,China)

机构地区：[1]遵义医科大学附属医院麻醉科,贵州遵义563300

出　　处：《中国病理生理杂志》2022年第1期74-79,共6页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81960214,No.82160223)。

摘　　要：目的:探讨七氟烷(Sev)对衰老模型大鼠认知能力及大脑前额叶皮质炎症因子表达的影响。方法:48只4月龄雄性SD大鼠,于大鼠头颈部皮下注射D-半乳糖(125 mg·kg-1·d-1)持续42 d建立衰老大鼠模型,按随机数字表法分为4组:空白对照(Con)组、核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)炎症小体抑制剂MCC950组、Sev组和MCC950治疗(Sev+MCC950)组,每组12只。水迷宫实验评估每组大鼠学习和工作记忆能力;HE染色法观察每组大鼠肺组织和大脑前额叶皮质区神经元形态;Western blot检测前额叶皮质离子钙结合接头分子1(Iba-1)、NLRP3、caspase-1、含caspase募集结构域的凋亡相关斑点样蛋白(ASC)、白细胞介素1β(IL-1β)和IL-18蛋白表达情况;ELISA检测检测大鼠大脑前额叶皮质及血清中炎症因子IL-1β和IL-18水平。结果:与Con组相比,Sev组大鼠逃避潜伏期显著增加,逃逸平台次数显著降低(P<0.05),大脑前额叶皮质区神经元显著损伤,前额叶皮质Iba-1、NLRP3、caspase-1、IL-1β和IL-18蛋白表达显著增加(P<0.05),中枢及外周IL-1β和IL-18炎症因子水平显著升高(P<0.05)。与Sev组相比,Sev+MCC950组大鼠学习和工作记忆能力显著提高(P<0.05),前额叶皮质Iba-1、NLRP3、caspase-1、IL-1β和IL-18蛋白表达水平显著下降(P<0.05),中枢及外周炎症因子水平显著降低(P<0.05)。结论:Sev致衰老模型大鼠认知功能障碍及前额叶皮质内神经炎症,其机制可能与Sev活化小胶质细胞NLRP3炎症小体,进而诱导IL-1β和IL-18炎症因子水平升高有关。AIM:To investigate the effects of sevoflurane(Sev)on cognitive function and expression of prefrontal cortex inflammatory factors in a rat aging model.METHODS:D-galactose(125 mg·kg-1·d-1)was subcutaneously injected into the head and neck of the rats for consecutive 42 d to establish the aging model. The rats were randomly allocated to 4 groups including blank control(Con)group,nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)inflammasome inhibitor MCC950 group,Sev group and MCC950 treatment(Sev+MCC950)group. The learning and working memory abilities of the rats were evaluated by water maze test. The morphological changes of neurons in the lung tissue and prefrontal cortex were observed by HE staining. The protein expression levels of ionized calcium-binding adaptor molecule-1(Iba-1),NLRP3,caspase-1,apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC),interleukin-1β(IL-1β)and IL-18 in the prefrontal cortex were detected by Western blot. The levels of IL-1β and IL-18 in the prefrontal cortex and serum of the rats were detected by ELISA.RESULTS:Compared with Con group,the rats in Sev group showed increased escape latency,decreased number of escape platform(P<0. 05),obvious damage in the prefrontal cortex neurons,as well as up-regulation of Iba-1,NLRP3,caspase-1,IL-1β and IL-18 in the central and peripheral regions(P<0. 05). Compared with Sev group,the learning and working memory ability was significantly improved,the protein expression of Iba-1,NLRP3,caspase-1,IL-1β and IL-18 was significantly down-regulated,and the levels of central and peripheral inflammatory factors were significantly decreased in Sev+MCC950 group(P<0. 05).CONCLUSION:The pathogenesis of cognitive dysfunction and the expression of neuroinflammatory factors in the prefrontal cortex in Sev-induced aging model rats may be related to the activation of NLRP3 inflammasome in microglia and the increases in IL-1β and IL-18 inflammatory factors.

关 键 词：七氟烷 NLRP3炎症小体 MCC950 术后认知功能障碍 前额叶皮质 

分 类 号：R749[医药卫生—神经病学与精神病学] R363[医药卫生—临床医学]