基于Nrf2/RAGE/NF-κB信号通路探究丙泊酚对帕金森病大鼠认知障碍的影响  

Effect of propofol on cognitive impairment in rats with Parkinson′s disease based on Nrf2/RAGE/NF-κB signal pathway

作　　者：高青 秦燕 任晓亮 宋琼远 GAO Qing;QIN Yan;REN Xiaoliang;SONG Qiongyuan(Department of Anesthesiology,Jinan Hospital of Integrated Traditional Chinese and Western Medicine,Jinan 271100,China)

机构地区：[1]济南市中西医结合医院麻醉科,山东济南271100

出　　处：《西部医学》2023年第12期1745-1750,共6页Medical Journal of West China

基　　金：济南市科技创新发展计划(202134063)。

摘　　要：目的探讨丙泊酚对帕金森病(PD)大鼠认知障碍及核因子E2相关因子2(Nrf2)通路与糖基化终末产物受体/核因子-κB(RAGE/NF-κB)信号通路的影响。方法腹腔注射MPTP制备PD大鼠模型。按照随机数字表法将60只SPF级雄性SD大鼠分为对照组(Control组)、模型组(PD组)、丙泊酚低、高剂量治疗组(Propofol-L组、Propofol-H组,分别用25、50 mg/kg丙泊酚腹腔注射)。Morris水迷宫实验与Y迷宫实验检测大鼠认知功能,HE染色观察脑黑质区病理变化,试剂盒检测脑黑质区氧化应激因子(SOD、CAT、MDA)、炎症因子水平(TNF-α、IL-1β),免疫荧光染色检测脑黑质区酪氨酸羟化酶(TH),Western blot检测RAGE、p-NF-κB p65、Nrf2、HO-1蛋白表达。结果与Control组比较,PD组大鼠逃避潜伏期增加,目标象限滞留时间百分比、穿过目标象限的次数、自发交替率明显减少(P<0.05),脑组织病理改变,脑黑质区MDA活性及TNF-α、IL-1β水平、RAGE、p-NF-κB p65蛋白表达水平显著增加,CAT、SOD活性及TH、Nrf2、HO-1蛋白表达水平显著降低(P<0.05);与PD组比较,Propofol-L组与Propofol-H组大鼠逃避潜伏期减少,目标象限滞留时间百分比、穿过目标象限的次数、自发交替率明显增加(P<0.05),脑组织病变减轻,脑黑质区MDA活性及TNF-α、IL-1β水平、RAGE、p-NF-κB p65蛋白表达显著降低,CAT、SOD活性及TH、Nrf2、HO-1蛋白表达显著升高,且呈剂量依赖性(P<0.05)。结论丙泊酚可改善PD大鼠认知障碍,其机制可能与激活Nrf2信号通路,抑制RAGE/NF-κB信号通路有关。Objective To investigate the influences of propofol on cognitive impairment,nuclear factor E2-related factor 2(Nrf2)pathway and receptor for advanced glycation end product/nuclear factor-κB(RAGE/NF-κB)signaling pathway in rats with Parkinson′s disease(PD).Methods PD rat model was established by intraperitoneal injection of MPTP.The rats were divided into control group(Control group),model group(PD group),low and high dose propofol treatment groups(Propofol-L group,Propofol-H group,25 and 50 mg/kg propofol intraperitoneal injection),according to the method of random number table.Morris water maze test and Y-maze test were performed to detect cognitive function in rats.HE staining was used to observe the pathological changes in the substantia nigra.The levels of oxidative stress factors and inflammatory factors and the protein expressions of tyrosine hydroxylase(TH),RAGE,p-NF-κB p65,Nrf2 and HO-1 in the substantia nigra were detected.Results Compared with the control group,the escape latency of the PD group increased,the percentage of residence time in the target quadrant,the number of crossing the target quadrant,and the rate of spontaneous alternation were significantly reduced(P<0.05),the pathological changes occurred in brain tissue,the MDA activity,the levels of TNF-αand IL-1β,and the protein expressions of RAGE,p-NF-κB p65 in the substantia nigra were significantly increased,and the activities CAT of SOD and the protein expressions of TH,Nrf2 and HO-1 were significantly decreased(P<0.05).Compared with PD group,the escape latency of rats in Propofo-L and Propofo-H groups was decreased,the percentage of retention time in the target quadrant,the number of crossing the target quadrant and the spontaneous alternations rate were increased significantly(P<0.05),and the lesions of brain tissue were reduced.MDA activity,TNF-αand IL-1βlevels,RAGE and P-NF-κB p65 protein expression were significantly decreased in the substantia nigra,while CAT and SOD activities and TH,Nrf2 and HO-1 protein expressions were s

关 键 词：丙泊酚 帕金森病 认知障碍 核因子E2相关因子2通路 糖基化终末产物受体/核因子-κB通路 

分 类 号：R-33[医药卫生] R742.5