己酮可可碱灌胃对急性肝性脑病大鼠脑水肿的改善作用及其机制  

Effect and mechanism of intragastric administration of pentoxifylline on brain edema in rats with acute hepatic encephalopathy

作　　者：罗妙莎 罗玉梅 冯云 和水祥[1] LUO Miaosha;LUO Yumei;FENG Yun;HE Shuixiang(Department of Gastroenterology,The First Affiliated Hospital of Xi'an Jiaotong University,Xi'an 710061,China)

机构地区：[1]西安交通大学第一附属医院消化内科,西安710061

出　　处：《山东医药》2023年第21期5-10,共6页Shandong Medical Journal

基　　金：陕西省重点研发计划项目(2021ZDLSF02-06);西安交通大学第一附属医院科研基金面上项目(2020ZYTS-15)。

摘　　要：目的观察己酮可可碱灌胃对急性肝性脑病大鼠脑水肿的改善作用,并探讨其作用机制。方法将60只雄性SD大鼠随机分为对照组、模型组、己酮可可碱低剂量组、己酮可可碱中剂量组、己酮可可碱高剂量组,每组12只。实验第1~3天,模型组、己酮可可碱低剂量组、己酮可可碱中剂量组、己酮可可碱高剂量组给予硫代乙酰胺连续腹腔注射3 d,制备急性肝性脑病大鼠模型;对照组给予等体积生理盐水腹腔注射。实验第4天起,己酮可可碱低剂量组、己酮可可碱中剂量组、己酮可可碱高剂量组大鼠分别给予己酮可可碱50、100、200 mg/(kg·d)灌胃,模型组及对照组给予等体积蒸馏水灌胃,连续7 d。观察各组大鼠实验期间饮食、运动等一般情况,称取灌胃结束后大鼠体质量。灌胃结束后,采用高架十字实验观察各组大鼠精神状态,采用开场实验观察各组大鼠自发运动能力(大鼠平均每分钟自发运动距离以及中央活动时间百分比),采用Morris水迷宫实验观察各组大鼠空间学习记忆能力(寻台潜伏期),使用全自动生化分析仪检测各组大鼠血氨、ALT、AST。大鼠断头取脑后,观察各组大鼠血脑屏障通透性(大鼠脑内EB含量),测算各组大鼠脑组织含水量,分别采用实时定量PCR法和Western blotting法检测各组大鼠脑组织中水通道蛋白4(AQP4)mRNA和蛋白,采用ELISA法检测各组大鼠脑组织中TNF-α、IL-1β。结果与对照组相比,模型组大鼠活动减少、精神萎靡、食欲不振,对外界刺激反应迟钝,体质量减轻(P<0.05),开臂进入次数百分比、开臂滞留时间百分比分、平均每分钟自发运动距离、中央活动时间百分比均降低(P均<0.05),寻台潜伏期延长(P<0.05),血氨、ALT、AST水平均升高(P均<0.05),大鼠脑内EB含量、脑组织含水量、脑组织中AQP4 mRNA和蛋白相对表达量均升高(P均<0.05),脑组织中TNF-α、IL-1β水平均升高(P均<0.05)。与模型�Objective To investigate the effect and mechanism of intragastric administration of pentoxifylline(PTX)on brain edema in rats with acute hepatic encephalopathy.Methods Sixty male SD rats were divided into the control group,model group,low-dose PTX[50 mg/(kg•d)]group,medium-dose PTX group[100 mg/(kg•d)]and highdose PTX[200 mg/(kg•d)]group,with 12 rats in each group.From day 1 to day 3,rats in the model group,low-dose PTX group,medium-dose PTX group,and high-dose PTX group were given thioacetamide by intraperitoneal injection for 3 consecutive days to establish the rat models of acute hepatic encephalopathy.Rats in the control group were given the same volume of normal saline through intraperitoneal injection.From the 4th day of the experiment,rats in the low-dose,medium-dose,and high-dose PTX groups were given 50,100,and 200 mg/(kg•d)PTX by gavage,respectively,and rats in the model group and control group were given the same volume of distilled water by gavage for 7 consecutive days.The diet,exercise and other general conditions of rats in each group during the experiment were observed,and the body weight of rats after gavage was measured.After gavage,the mental state of rats in each group was observed by the elevated plus maze,the spontaneous movement ability(the average spontaneous movement distance per minute of rats and the percentage of central activity time)was observed by the open field test,and the spatial learning and memory ability(the platform finding latency)was observed by the Morris water maze.Blood ammonia,alanine aminotransferase(ALT)and aspartate aminotransferase(AST)were detected by automatic biochemical analyzer.After the rats were decapitated,the permeability of blood-brain barrier(EB content in rat brain)was observed,the water content of brain tissues was measured,and the aquaporin 4(AQP4)mRNA and protein in the brain tissues were detected by real-time quantitative PCR and Western blotting.The levels of tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)in the brain tissues wer

关 键 词：己酮可可碱 肝性脑病 急性肝性脑病 脑水肿 水通道蛋白4 动物实验 

分 类 号：R575.2[医药卫生—消化系统]