Nrf2/HO-1信号通路在依达拉奉减轻长期丙泊酚镇静致新生大鼠远期认知功能障碍中的作用  

Role of Nrf2/HO-1 signaling pathway in edaravone-induced attenuation of long-term cognitive impairment caused by long-time sedation with propofol in neonatal rats

作　　者：刘扬[1] 张琦 崔建利 陈岩[1] 刘祥[1] 赵海涛[1] 石磊[1] Liu Yang;Zhang Qi;Cui Jianli;Chen Yan;Liu Xiang;Zhao Haitao;Shi Lei(Department of Anesthesiology,Hebei Children′s Hospital,Shijiazhuang 050031,China)

机构地区：[1]河北省儿童医院麻醉科,石家庄050031

出　　处：《中华麻醉学杂志》2023年第6期736-740,共5页Chinese Journal of Anesthesiology

基　　金：河北省医学科学研究课题计划项目(20220712);河北省自然科学基金(H2022316001)。

摘　　要：目的评价核因子E2相关因子2(Nrf2)/血红素加氧酶-1(HO-1)信号通路在依达拉奉减轻长期丙泊酚镇静致新生大鼠远期认知功能障碍中的作用。方法SPF级健康新生SD大鼠80只,7日龄,体质量15~20 g,雌雄不拘,采用随机数字表法分为4组(n=20):对照组(C组)、丙泊酚组(P组)、依达拉奉+丙泊酚组(EP组)和Nrf2抑制剂ML385+依达拉奉+丙泊酚组(MEP组)。P组、EP组和MEP组腹腔注射丙泊酚75 mg/kg,C组腹腔注射等量中/长链脂肪乳注射液,1次/d,连续7 d。EP组和MEP组于每次注射丙泊酚前30 min时腹腔注射依达拉奉3 mg/kg,MEP组同时腹腔注射ML38515 mg/kg。于出生29 d时行旷场试验评估大鼠自发活动能力,于出生30~34 d时行Morris水迷宫实验检测大鼠认知功能。水迷宫结束后处死大鼠分离海马组织,采用流式细胞术检测ROS水平,ELISA法检测SOD和MDA水平,Western blot法测定Nrf2和HO-1表达,HE染色法观察海马CA1区病理学改变。结果4组旷场实验运动速度、路程以及旷场中心停留时间比较差异无统计学意义(P>0.05)。与C组比较,P组逃避潜伏期延长,穿越原平台位置次数减少,海马MDA及ROS水平升高,SOD活性下降,Nrf2和HO-1表达下调(P<0.05),海马CA1区发生病理学损伤;与P组比较,EP组逃避潜伏期缩短,穿越原平台位置次数增加,海马MDA及ROS水平下降,SOD活性升高,Nrf2和HO-1表达上调(P<0.05),海马CA1区病理学损伤减轻;与EP组比较,MEP组逃避潜伏期缩延长,穿越原平台位置次数减少,海马MDA及ROS水平升高,SOD活性下降,Nrf2和HO-1表达下调(P<0.05),海马CA1区病理学损伤加重。结论依达拉奉减轻长期丙泊酚镇静致新生大鼠远期认知功能障碍的机制与激活Nrf2/HO-1信号通路,抑制氧化应激水平有关。Objective To evaluate the role of nuclear factor E2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)signaling pathway in edaravone-induced attenuation of long-term cognitive impairment caused by long-time sedation with propofol in the neonatal rats.Methods Eighty SPF healthy newborn Sprague-Dawley rats of both sexes,aged 7 days,weighing 15-20 g,were divided into 4 groups(n=20 each)using a random number table method:control group(group C),propofol group(group P),edaravone+propofol group(group EP)and Nrf2 inhibitor ML385+edaravone+propofol group(group MEP).Propofol 75 mg/kg was intraperitoneally injected once a day for 7 consecutive days in P group,EP group and MEP group,respectively,while the equal volume of medium/long chain fat emulsion injection was intraperitoneally injected in C group.Edaravone 3 mg/kg was intraperitoneally injected at 30 min before each propofol injection in EP and MEP groups,and ML38515 mg/kg was intraperitoneally injected simultaneously in group MEP.The spontaneous activity was evaluated by the open field test on day 29 after birth,and the cognitive function was assessed by Morris water maze test on days 30-34 after birth.The rats were sacrificed after the end of water maze test,and brains were removed and hippocampal tissues were obtained for determination of reactive oxygen species(ROS)levels(by flow cytometry),superoxide dismutase(SOD)and malondialdehyde(MDA)levels(by enzyme-linked immunosorbent assay)and expression of Nrf2 and HO-1(by Western blot)and for microscopic examination of the pathological changes in the hippocampal CA1 area(using HE staining).Results There was no significant difference in the speed,distance and time of stay at the center of the open field among the four groups(P>0.05).Compared with C group,the escape latency was significantly prolonged,the number of crossing the original platform quadrant was reduced,the levels of MDA and ROS were increased,the activity of SOD was decreased,the expression of Nrf2 and HO-1 was down-regulated(P<0.05),and the pathological injury wa

关 键 词：依达拉奉 二异丙酚 婴儿 新生 认知功能障碍 NF-E2相关因子2 血红素加氧酶-1 

分 类 号：R614[医药卫生—麻醉学]