胃促生长素对脓毒症大鼠脑功能障碍的影响及相关机制.doc

胃促生长素对脓毒症大鼠脑功能障碍的影响及相关机制 魏华 封小美 薛庆生 张富军 于布为 【摘要】 目的 探讨炎症因子在脓毒症大鼠脑功能障碍发病机制中的作用以及胃促生长素（ghrelin）对脓毒症大鼠脑功能和脑部炎症反应的影响。方法 64只雄性SD大鼠随机分为四组：假手术组（Sham组，n=16）、假手术+ghrelin组（Sham+ghrelin组，n=16）、脓毒症脑病组（CLP组，n=16）和脓毒症脑病+ ghrelin组（CLP+ghrelin组，n=16）。采用盲肠结扎穿孔法（CLP）制作大鼠脓毒症脑病模型。Sham+ghrelin组和CLP+ghrelin组于造模后即刻及12h后腹腔注射ghrelin 80 μg/kg，Sham组及CLP组于相应时间点腹腔注射等量0.9%氯化钠溶液。将每组再分为三个亚组：第一亚组（n=6），于术后6h采用动物神经功能评分表对大鼠进行评分，而后麻醉断头取左侧海马组织ELISA法测炎症因子TNF-α及IL-6；第二亚组（n=6），于术后24h进行上述处理；第三亚组（n=4），于24h时灌注取脑组织进行尼氏染色行病理学观察。结果 与Sham组和Sham+ghrelin组相比，CLP组和CLP+ghrelin组术后6h和24h时TNF-α及IL-6水平均显著升高（P值﹤0.05）；6h时大鼠神经功能评分无差异（P值0.05），24h时神经功能评分降低（P值﹤0.05）；海马神经元尼氏染色病理变化明显。CLP+ghrelin组与CLP组相比，术后6h和24h时 TNF-α及IL-6的表达均显著降低（P值﹤0.05），海马区神经元损伤减轻，大鼠神经功能评分显著升高（P值﹤0.05）。结论 ghrelin对脓毒症大鼠脑功能起到一定保护作用，其机制可能与下调炎症因子TNF-α及IL-6的表达而减轻海马神经元的损伤有关。 【关键词】 ghrelin；脓毒症脑病；炎症因子；神经元丢失 Effects of ghrelin on brain dysfunction during CLP-induced rats sepsis and the related mechanisms WEI Hua，FENG Xiaomei， XUE Qingsheng，ZHANG Fujun，YU Buwei. Department of Anesthesiology , Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200025, China Corresponding author: ZHANG Fujun EMAIL：fujunzhang1964@ 【Abstract】 Objective To investigate the effects of ghrelin on brain dysfunction and inflammatory cytokines in cecal ligation and puncture (CLP)-induced rats sepsis and the role of inflammatory cytokines in their pathogenesis. Methods Sixty-four male SD rats were randomly divided into 4 groups: sham group (n=16), sham+ghrelin group (n=16), CLP group (n=16) and CLP+ghrelin group (n=16). The septic encephalopathic rat model was established by CLP. Ghrelin (80 μg/kg) was administered by intraperitoneal injection immediately and 12 hours after operation in Sham+ghrelin group and CLP+ghrelin group. The same volume of normal saline was given in Sham group and CLP group at the same time. Each group was randomly divided into three subgroups: the first subgroup contained 6 rats, which were performed by neurologically assessment 6 hours after C