NRG1/ErbB4通路在七氟醚诱导大鼠认知功能障碍中的作用  

Role of NRG1/ErbB4 pathway in sevoflurane⁃induced cognitive dysfunction in rats

作　　者：于绍勇 傅麟 俞洪韵 李波 张世民 江慧洪 YU Shao-yong;FU Lin;YU Hong-yun;LI Bo;ZHANG Shi-min;JIANG Hui-hong(Department of Anesthesiology,Yangpu Hospital,Tongji University,Shanghai 200090,China;Department of Orthopedics,Yangpu Hospital,Tongji University,Shanghai 200090,China;Department of General Surgery,Yangpu Hospital,Tongji University,Shanghai 200090,China)

机构地区：[1]上海同济大学附属杨浦医院麻醉科,上海200090 [2]上海同济大学附属杨浦医院骨科,上海200090 [3]上海同济大学附属杨浦医院普外科,上海200090

出　　处：《解剖学研究》2024年第4期303-309,共7页Anatomy Research

基　　金：上海市浦江人才计划(21PJD066)。

摘　　要：目的 探讨神经调节蛋白1(NRG1)/ErbB4通路在七氟醚诱导的大鼠认知功能障碍中的作用。方法 48只SD大鼠随机分为对照组、七氟醚组、七氟醚+NRG1-β1(NRG1类似物,5μg/kg)组、七氟醚+NRG1-β1+AG1478(ErbB4受体阻断剂,2.5微克/只)组,每组12只。大鼠喂养至第14天,Morris水迷宫实验测定各组大鼠认知功能,苏木精-伊红染色(HE)染色观察海马组织神经元状态,原位细胞凋亡法(TUNEL)检测海马组织神经元凋亡情况,酶联免疫吸附(ELISA)法测定海马组织炎症因子表达水平,WB检测海马组织凋亡相关蛋白及NRG1/ErbB4通路相关蛋白表达。结果 与对照组相比,七氟醚组大鼠潜伏期明显增加,穿台次数和目标象限停留时间明显降低,认知功能、海马组织严重受损,海马组织神经细胞凋亡率[七氟醚组(30.17±6.29)%、对照组(3.06±0.63)%]、炎症因子水平及凋亡相关蛋白表达明显增加,NRG1(七氟醚组0.21±0.04、对照组1.03±0.15)、p-ErbB4/ErbB4(七氟醚组0.19±0.03、对照组0.98±0.10)显著降低,差异均有统计学意义(P<0.05);与七氟醚组相比,七氟醚+NRG1-β1组大鼠认知功能、海马组织损伤得到缓解,海马组织神经元细胞凋亡率[(12.61±2.61)%比(30.17±6.29)%]、凋亡相关蛋白表达、炎症因子水平显著降低,NRG1(0.79±0.12比0.21±0.04)、p-ErbB4/ErbB4(1.27±0.13比0.19±0.03)显著升高(P<0.05);AG1478逆转了NRG1-β1对七氟醚诱导的大鼠认知功能障碍的减轻作用。结论 NRG1/ErbB4通路在七氟醚诱导大鼠认知功能障碍中发挥重要作用,可能激活NRG1/ErbB4通路以改善大鼠认知功能障碍。Objective To investigate the role of neuregulin 1(NRG1)/ErbB4 pathway in sevoflurane-induced cognitive impairment in rats.Methods Thirty-two SD rats were randomly divided into control group,sevoflurane group,sevoflurane+NRG1-β1(NRG1 analogue,5μg/kg)group,sevoflurane+NRG1-β1+AG1478(ErbB4 receptor blocker,2.5μg/rat)group,with 12 rats in each group.The rats were fed until day 14,Morris water maze test was used to measure the cognitive function,hematoxylin-eosin staining(HE)was used to observe the neurons in hippocampus,apoptosis of hippocampal neurons was detected by TUNEL,ELISA was used to determine the expression of inflammatory factors in hippocampus,WB was used to detect the expression of apoptosis related proteins and NRG1/ErbB4 pathway related proteins in hippocampus.Results Compared with control group,the latency of sevoflurane group was significantly increased,and the number of times of crossing platform and the residence time in the target quadrant was significantly decreased,the cognitive function and hippocampus were seriously damaged,the apoptosis rate(30.17%±6.29%vs.3.06%±0.63%)in hippocampus,the level of inflammatory factors and the expression of apoptosis related proteins were significantly increased,the expression of NRG1(0.21±0.04 vs.1.03±0.15)and p-ERBB4/ErbB4(0.19±0.03 vs.0.98±0.10)was significantly decreased(all P<0.05).Compared with sevoflurane group,the cognitive function and hippocampal tissue damage in sevoflurane+NRG1-β1 group were alleviated,the apoptosis rate of hippocampal neurons(12.61%±2.61%vs.30.17%±6.29%),the expression of apoptosis related proteins and the level of inflammatory factors were significantly decreased,the expression of NRG1(0.79±0.12 vs.0.21±0.04)and p-ErbB4/ErbB4(1.27±0.13 vs.0.19±0.03)was significantly increased(P<0.05).AG1478 reversed the alleviating effect of NRG1-β1 on sevoflurane induced cognitive dysfunction in rats.Conclusion NRG1/ErbB4 pathway plays an important role in sevoflurane-induced cognitive dysfunction in rats.Activation of NRG1/ErbB4

关 键 词：神经调节蛋白1 七氟醚 受体蛋白酪氨酸激酶erbB-4 认知功能障碍 

分 类 号：R614[医药卫生—麻醉学]