白桦脂酸对异氟醚诱导的发育期大鼠神经细胞损伤的保护作用  

Protective effect of betulinic acid against isoflurane induced neuronal damage in developing rats

作　　者：王东伟[1] 刘海萍[1] 王庆东 赫赤[1] 刘思洋[1] 胡玉红[2] 陈萍[2] 臧荣佳[1] WANG Dong-wei;LIU Hai-ping;WANG Qing-dong;HE Chi;LIU Si-yang;HU Yu-hong;CHEN Ping;ZANG Rong-jia(Department of Anesthesiology,the First Affiliated Hospital of Jiamusi University,Jiamusi 154002,China;Department of Obstetrics and Gynecology,the First Affiliated Hospital of Jiamusi University,Jiamusi 154002,China)

机构地区：[1]佳木斯大学附属第一医院麻醉科,黑龙江佳木斯154002 [2]佳木斯大学附属第一医院妇产科,黑龙江佳木斯154002

出　　处：《中国药理学与毒理学杂志》2021年第6期438-443,共6页Chinese Journal of Pharmacology and Toxicology

基　　金：佳木斯大学博士专项科研基金启动项目(JMSUBZ2019-05);黑龙江省中医药科研项目(ZHY2020-177);黑龙江省卫生健康委科研课题(2018-328);黑龙江省卫生健康委科研课题(2020-344)。

摘　　要：目的观察白桦脂酸(BC)对异氟醚(Iso)诱导的发育期大鼠神经细胞损伤的保护作用。方法7日龄SD大鼠80只,随机分为正常对照组、Iso组、Iso+BC 100和200 mg·kg^(-1)组。除正常对照组外,其余各组置麻醉箱内吸入1.5%Iso 6 h麻醉。麻醉前1 h分别ip给予生理盐水(正常对照组和Iso组)或不同剂量BC预处理。麻醉完毕后立即进行动脉血气分析。而后,每组随机取10只大鼠处死并取海马,流式细胞术检测大鼠海马神经细胞凋亡;硫代巴比妥酸法检测海马组织匀浆中丙二醛(MDA)含量;DCFH-DA染色法测定海马神经细胞中活性氧(ROS)水平,JC-1染色法检测线粒体膜电位(MMP),Fluo-3/AM探针法测定神经细胞内游离Ca^(2+) 浓度。每组另10只大鼠继续饲养6周后,用Morris水迷宫实验检测大鼠学习记忆能力。结果各组大鼠血液pH值、p O2和p CO2均无明显差异。与正常对照组比较,Iso组大鼠海马神经细胞凋亡率显著升高(P<0.01),海马组织中MDA含量、海马神经细胞内ROS水平和游离Ca^(2+) 浓度显著升高(P<0.01),海马神经细胞MMP明显降低(P<0.01);Morris水迷宫实验潜伏期延长(P<0.01),穿越平台次数减少(P<0.01),空间搜索时间减少(P<0.01)。与Iso组相比,Iso+BC 100和200 mg·kg^(-1)组大鼠海马神经细胞凋亡率、海马组织中MDA含量、海马神经细胞内ROS水平和Ca^(2+) 浓度均显著降低(P<0.05),MMP显著升高(P<0.05);Morris水迷宫实验潜伏期缩短(P<0.05),穿越平台次数增加(P<0.05),空间搜索时间延长(P<0.05)。结论BC预处理能够改善Iso暴露诱导的发育期大鼠海马神经细胞凋亡和氧化损伤及空间记忆功能障碍。OBJECTIVE To observe the effect of betulinic acid(BC)on isoflurane(Iso)-induced neuronal damage in developing rats.METHODS Eighty newborn seven-day-old SD rats were randomly divided into four groups:normal control,Iso,Iso+BC 100 and 200 mg·kg^(-1) groups.Rats were inhaled1.5%Iso for 6 h exposure anesthesia except those in normal control group.Rats were ip given 0.9%normal saline(the normal control and Iso)or BC 100 and 200 mg·kg^(-1)(Iso+BC groups)1 h before anesthesia before being subjected to arterial blood gas analysis.Ten rats were randomly selected from each group for sacrifice and hippocampus collection.The apoptosis of hippocampal neurons was detected by flow cytometry,the content of malondialdehyde(MDA)in hippocampal neurons was determined by using thiobarbituric acid,and the levels of reactive oxygen species(ROS),mitochondrial membrane potential(MMP)and intracellular free Ca^(2+) in neurons were measured by fluorescence assay.The remaining 10 rats in each group were raised for another 6 weeks and Morris water(MWM)maze was used to observe the learning and cognitive ability of rats.RESULTS There was no significant difference in pH,p O2 or p CO2 between the four groups.Compared with the normal control group,the apoptosis rate of hippocampal neurons,MDA content in hippocampal tissues,the ROS level and intracellular free Ca^(2+) concentration in hippocampal neurons in Iso group were significantly increased(P<0.01)while the MMP of hippocampal neurons in Iso group was significantly decreased(P<0.01).In MWM test,the latency time in Iso group was prolonged(P<0.01),the number of times corossing the platform was decreased(P<0.01),and the space search time was significantly shortened(P<0.01).Compared with Iso group,the apoptosis rate of hippocampal neurons,MDA content in hippocampal tissues,the ROS level and intracellular free Ca^(2+) concentration in the hippocampus in Iso+BC 100 and 200 mg·kg^(-1) groups were decreased(P<0.05),the MMP of hippocampal neurons in Iso+BC 100 and 200 mg·kg^(-1) groups was significa

关 键 词：白桦脂酸 异氟醚 氧化损伤 细胞凋亡 

分 类 号：R964[医药卫生—药理学]