瘦素对原位肝移植术大鼠脑损伤时海马细胞焦亡的影响  

Effect of leptin on pyroptosis in hippocampal cells during brain injury in a rat model of orthotopic liver transplantation

作　　者：孙帅[1] 刘艳萍[1] 杨光辉[1] 李红军[1] Sun Shuai;Liu Yanping;Yang Guanghui;Li Hongjun(Department of Anesthesiology,Zhengzhou People′s Hospital,Zhengzhou 450002,China)

机构地区：[1]郑州人民医院麻醉科,450002

出　　处：《中华麻醉学杂志》2020年第3期312-315,共4页Chinese Journal of Anesthesiology

摘　　要：目的评价瘦素对原位肝移植术大鼠脑损伤时海马细胞焦亡的影响。方法清洁级健康雄性SD大鼠54只,12周龄,体重200~250 g,采用随机数字表法分为3组(n=18):假手术组(S组)、原位肝移植术大鼠脑损伤组(Liver组)和瘦素组(Lep组)。Liver组和Lep组建立原位肝脏移植术大鼠脑损伤模型,S组只开腹游离肝周韧带,Lep组于门静脉阻断即刻腹腔注射瘦素1 mg/kg,S组和Liver组同时点腹腔注射等量生理盐水。于术后第3天每组随机取12只大鼠处死并取海马,光镜下观察病理学结果,采用RT-PCR法检测NLRP3、caspase-1、IL-1β、IL-18和GSDMD的mRNA的表达,Western blot法检测NLRP3、caspase-1、IL-1β、IL-18和GSDMD的表达;于术后第30天每组余6只大鼠行Morris水迷宫实验。结果与S组比较,Liver组和Lep组海马存活神经元计数降低,NLRP3、caspase-1、IL-1β、IL-18及GSDMD及其mRNA表达上调,平台所在象限滞留时间缩短,逃避潜伏期延长(P<0.05);与Liver组比较,Lep组海马存活神经元计数升高,NLRP3、caspase-1、IL-1β、IL-18及GSDMD及其mRNA表达下调,平台所在象限滞留时间延长,逃避潜伏期缩短(P<0.05)。Lep组海马组织病理学损伤较Liver组减轻。结论瘦素减轻原位肝移植术大鼠脑损伤的机制与抑制海马细胞焦亡有关。Objective To evaluate the effect of leptin on pyroptosis in hippocampal cells during brain injury in a rat model of orthotopic liver transplantation(OLT).Methods Fifty-four clean-grade male Sprague-Dawley rats,aged 12 weeks,weighing 200-250 g,were divided into 3 groups(n=18 each)by a random number table method:sham operation group(S group),OLT-induced brain injury group(Liver group)and leptin group(Lep group).The model of OLT was established according to the"two-cuff"technique in anesthetized rats in Liver and Lep groups.The perihepatic ligament was only isolated and freed in S group.Leptin 1 mg/kg was intraperitoneally injected immediately after portal vein occlusion in Lep group.The equal volume of normal saline was intraperitoneally injected at the same time point in S group and Liver group.Twelve rats in each group were selected on day 3 after surgery and sacrificed,and the hippocampal tissues were obtained for examination of the pathological changes(with a light microscope)and for determination of the expression of NOD-like receptor protein 3(NLRP3),caspase-1,interleukin-1beta(IL-1β),IL-18 and gasdermin D(GSDMD)mRNA(by real-time polymerase chain reaction)and expression of NLRP3,caspase-1,IL-1β,IL-18 and GSDMD(by Western blot).Morris water maze test was performed in the remaining 6 rats in each group on day 30 after surgery.Results Compared with S group,the count of viable neurons in hippocampi was significantly decreased,the expression of NLRP3,caspase-1,IL-1β,IL-18 and GSDMD protein and mRNA was up-regulated,the time of staying at the platform quadrant was shortened,and the escape latency was prolonged in Liver and Lep groups(P<0.05).Compared with Liver group,the count of viable neurons in hippocampi was significantly increased,the expression of NLRP3,caspase-1,IL-1β,IL-18 and GSDMD protein and mRNA was down-regulated,the time of staying at the platform quadrant was prolonged,and the escape latency was shortened in Lep group(P<0.05).The pathological changes of hippocampal tissues were significantly atte

关 键 词：瘦素 肝移植 脑损伤 海马 细胞焦亡 

分 类 号：R657.3[医药卫生—外科学]