右美托咪定通过激活PI3K/AKT信号通路对前列腺素诱导分娩窒息子鼠氧化应激和炎症水平的影响及脑保护机制  

Effects of dexmedetomidine on oxidative stress and inflammation levels in prostaglandin induced asphyxiat⁃ed offspring by activating PI3K/AKT signaling pathway and its role in brain protection

作　　者：葛亮 冷玉芳[2] 张鹏 杜丽芳[1] 韩旭东[1] GE Liang;LENG Yufang;ZHANG Peng;DU Lifang;HAN Xudong(Gansu Maternal and Child Health Hospital,Lanzhou 730050,China)

机构地区：[1]甘肃省妇幼保健院(甘肃省中心医院),兰州730050 [2]兰州大学第一医院,兰州730000

出　　处：《实用医学杂志》2023年第6期688-695,共8页The Journal of Practical Medicine

基　　金：甘肃省自然科学基金项目(编号:20JR10RA423)。

摘　　要：目的探讨右美托咪定通过激活PI3K/AKT信号通路对前列腺素诱导分娩窒息子鼠氧化应激和炎症水平的影响及脑保护机制。方法将孕鼠随机分为对照组、模型组、右美托咪定低剂量组、右美托咪定高剂量组、右美托咪定+LY294002组。对照组孕鼠自然分娩,模型组与给药组孕鼠构建分娩窒息模型,分组处理孕鼠后分娩,每组选出12只子鼠检测其学习记忆能力、海马神经元损伤凋亡、脑组织超氧化物歧化酶(SOD)、丙二醛(MDA)、环氧化酶-2(COX-2)及白细胞介素-6(IL-6)水平、脑组织自噬及PI3K/AKT通路相关蛋白表达。结果与对照组相比,模型组子鼠海马神经元发生严重损伤,神经元凋亡率、脑组织MDA、COX-2及IL-6水平、LC3-II/LC3-I及Beclin-1、P62表达明显升高(P<0.05),目标象限停留时间、穿越原平台位置次数、神经元数量、脑组织SOD水平及p-PI3K/PI3K、p-Akt/Akt明显降低(P<0.05);与模型组相比,右美托咪定给药组子鼠海马神经元发生损伤均减轻,神经元凋亡率、脑组织MDA、COX-2及IL-6水平、LC3-II/LC3-I及Beclin-1、P62表达均降低(P<0.05),目标象限停留时间、穿越原平台位置次数、神经元数量、脑组织SOD水平及p-PI3K/PI3K、p-Akt/Akt均升高(P<0.05),且高剂量的右美托咪定作用更强;与右美托咪定高剂量组相比,右美托咪定+LY294002组子鼠各指标变化趋势发生逆转。结论右美托咪定可通过激活PI3K/AKT信号降低前列腺素诱导的分娩窒息新生子鼠氧化应激及炎症水平,抑制自噬,减轻子鼠海马神经元损伤及凋亡,改善其学习记忆功能,发挥脑保护作用。Objective To investigate the effects of dexmedetomidine on oxidative stress and inflammation in prostaglandin induced asphyxiated offspring by activating PI3K/AKT signal pathway and explore the mechanism of brain protection as well.Methods Pregnant rats were randomly grouped into model group,dexmedetomidine low⁃dose group,dexmedetomidine high⁃dose group,and dexmedetomidine+LY294002 group,the pregnant rats in the control group gave birth naturally,while the pregnant rats in the model group and the drug administration group were used to construct the asphyxia model of labor.After grouping,12 offspring rats were selected from each group to detect their learning and memory abilities,hippocampal neuron damage and apoptosis,levels of superoxide dismutase(SOD),malondialdehyde(MDA),cyclooxygenase⁃2(COX⁃2)and interleukin⁃6(IL⁃6)in the brain tissue,expression of autophagy and PI3K/AKT pathway⁃related proteins in brain tissue.Results Compared with the control group,the hippocampal neurons of offspring rats in the model group were severely damaged.The apoptosis rate,levels of MDA,COX⁃2 and IL⁃6 in brain tissue,and expression levels of LC3⁃II/LC3⁃I,Beclin⁃1 and P62 were obviously increased(P<0.05),residence time in the target quadrant,times of crossing the original platform,number of neurons,and levels of SOD and p⁃PI3K/PI3K and p⁃Akt/Akt in the brain tissue were obviously decreased(P<0.05).Compared with the model group,the damage of hippocampal neurons in the dexmedetomidine groups were alleviated.The apoptosis rate,levels of MDA,COX⁃2 and IL⁃6 in brain tissue,and expression levels of LC3⁃Ⅱ/LC3⁃Ⅰ,Beclin⁃1 and P62 were all decreased(P<0.05),residence time in the target quadrant,times of crossing the original platform,number of neurons,and levels of SOD and p⁃PI3K/PI3K and p⁃Akt/Akt in brain tissue were all increased(P<0.05),and high⁃dose dexmedetomidine had an even stronger effect.In addition,compared with the high⁃dose dexmedetomidine group,the trend of various indexes in dex

关 键 词：磷脂酰肌醇3-激酶/蛋白激酶B 自噬 右美托咪定 前列腺素 分娩窒息 脑保护 

分 类 号：R722.12[医药卫生—儿科]