盐酸戊乙奎醚对脑梗死模型大鼠的神经保护作用及机制  

Neuroprotective effect and mechanism of penehyclidine hydrochloride on model rats with cerebral infarction

作　　者：唐晓怡 谭红保[1] 赵倩[1] 李玉芳[1] 吴荻 TANG Xiao-yi;TAN Hong-bao;ZHAO Qian;LI Yu-fang;WU Di(Department of Anesthesiology,Changsha Fourth Hospital,Changsha 410000,China')

机构地区：[1]湖南省长沙市第四医院麻醉科,长沙市410000

出　　处：《广西医学》2021年第23期2829-2833,2844,共6页Guangxi Medical Journal

基　　金：湖南省自然科学基金(2020JJ8039)。

摘　　要：目的探讨盐酸戊乙奎醚对脑梗死模型大鼠的神经保护作用及相关机制。方法选取30只SD健康雄性大鼠,随机分为正常组、模型组、盐酸戊乙奎醚组各10只。取模型组、盐酸戊乙奎醚组大鼠建立脑梗死模型,随后给予盐酸戊乙奎醚组大鼠腹腔注射盐酸戊乙奎醚,给予对照组和模型组大鼠腹腔注射生理盐水。评定各组大鼠学习记忆能力、神经行为学评分,测定脑组织梗死体积、含水量。检测各组大鼠脑组织的氧化应激指标[过氧化氢酶(CAT)、活性氧簇(ROS)、8-羟基脱氧鸟苷(8-OHdG)]及炎症因子[白细胞介素(IL)-6、IL-1β]水平,以及脑组织Toll样受体4(TLR4)、核因子κB(NF-κB)、自噬相关蛋白[Beclin-1、微管相关蛋白1轻链3B(MAP1LC3B)]、凋亡相关蛋白[磷脂酰肌醇3-激酶(PI3K)、哺乳动物雷帕霉素靶蛋白(mTOR)]的表达量。结果 (1)随着训练时间延长各组大鼠逃避潜伏期逐渐缩短(均P<0.05);模型组、盐酸戊乙奎醚组、正常组大鼠各时间点逃避潜伏期依次缩短,神经行为学评分依次降低(均P<0.05)。(2)与模型组比较,盐酸戊乙奎醚组大鼠脑组织梗死体积缩小。模型组、盐酸戊乙奎醚组、正常组大鼠脑组织含水量依次减少(均P<0.05)。(3)模型组、盐酸戊乙奎醚组、正常组大鼠脑组织CAT水平依次升高,ROS、8-OHdG、IL-6、IL-1β水平依次降低,TLR4、NF-κB、Beclin-1、MAP1LC3B、PI3K、mTOR的蛋白相对表达量依次下降(均P<0.05)。结论盐酸戊乙奎醚不仅可缩小脑梗死大鼠的脑梗死体积、减轻脑水肿,还可改善大鼠的神经功能和认知功能。该药物的神经保护作用可能与其减轻氧化应激反应、调控TLR4/NF-κB通路及下游炎症因子以减轻炎症反应,以及调控相关蛋白以抑制神经细胞自噬和凋亡有关。Objective To explore the neuroprotective effect and related mechanism of penehyclidine hydrochloride on model rats with cerebral infarction.Methods Thirty healthy male SD rats were selected and randomly divided into normal group(n=10), model group(n=10) and penehyclidine hydrochloride group(n=10). Rats in the model and penehyclidine hydrochloride groups were selected to establish the models of cerebral infarction, then rats in the penehyclidine hydrochloride group were injected with penehyclidine hydrochloride intraperitoneally, and rats in the control and model groups were given an intraperitoneal injection of normal saline. The score for learning and memory ability and the neurobehavioral score of rats were assessed, and the infarction volume and the water content of brain tissues were determined in each group. The levels of oxidative stress indicators(catalase[CAT], reactive oxygen species[ROS], 8-hydroxy-2′-deoxyguanosine[8-OHdG]) and inflammatory factors(interleukin[IL]-6, IL-1β) in rat brain tissues, as well as the expression of Toll-like receptor 4(TLR4), nuclear factor κB(NF-κB), autophagy-related proteins(Beclin-1, microtubule-associated protein 1 light chain 3β[MAP1 LC3 B]), and apoptosis-related proteins(phosphatidylinositol-3-kinase[PI3 K] and mammalian target of rapamycin[mTOR]) in brain tissues, were detected in each group. Results(1)The escape latency period of rats decreased gradually with the increasing training time in each group(all P<0.05);the escape latency period and the neurobehavioral score decreased in the sequence of the model group, the penehyclidine hydrochloride group and the normal group at all time points(all P<0.05).(2)Compared with the model group, rats in the penehyclidine hydrochloride group had a decreased infarction volume of brain tissues. The water content of rat brain tissues decreased in the sequence of the model group, the penehyclidine hydrochloride group and the normal group(all P<0.05).(3)The CAT level in rat brain tissues increased, the levels of ROS, 8-OHdG, IL

关 键 词：脑梗死 盐酸戊乙奎醚 神经保护作用 氧化应激 炎症反应 自噬 凋亡 大鼠 

分 类 号：R743.33[医药卫生—神经病学与精神病学]