高压氧早期干预对创伤后应激障碍模型大鼠行为及海马核因子E2相关因子2和血红素加氧酶1表达水平的影响  

Effects of hyperbaric oxygen early intervention on the behavior change and the levels of Nrf2 and HO-1 in the hippocampus of post-traumatic stress disorder model rats

作　　者：薛芬[1] 薛姗姗[1] 周翠红[1] 于欢 彭正午[1] Xue Fen;Xue Shanshan;Zhou Cuihong;Yu Huan;Peng Zhengwu(Department of Psychiatry,Xijing Hospital,Fourth Military Medical University,Xi’an 710032,China)

机构地区：[1]第四军医大学西京医院心身科,西安710032

出　　处：《神经疾病与精神卫生》2020年第3期157-162,共6页Journal of Neuroscience and Mental Health

基　　金：国家自然科学基金项目(81904280)。

摘　　要：目的探讨高压氧早期干预对创伤后应激障碍(PTSD)模型大鼠行及海马核因子E2相关因子2(nuclear factor erythroid 2-related factor 2,Nrf2)及血红素加氧酶1(HO-1)基因表达的影响.方法将32只雄性Sprague-Dawley大鼠随机分为对照组(sham组)、高压氧组(HBO组)、模型组(ESPS组)、模型+高压氧早期干预组(ESPS+HBO组),每组8只.ESPS组和ESPS+HBO组大鼠经增强型单次延长应激(ESPS)构建PTSD模型,其他两组不接受ESPS造模,但置于同一实验室环境.造模结束24 h后,各组大鼠置于高压氧舱进行1 h高压氧(2.5个大气压,100%O2)或常压空气干预,连续5 d.干预结束后将大鼠放回原饲养笼中不受打扰饲养7 d.通过旷场实验、高架十字迷宫实验以及条件性恐惧性实验观察大鼠的行为表现,并通过蛋白免疫印迹法(Western Blot)检测大鼠海马组织Nrf2和HO-1的表达情况.结果(1)各处理组旷场内总运动距离的差异无统计学意义(P>0.05);ESPS组中心区运动时间[(20.52±9.25)s]和进入旷场中心区次数[(15.22±4.38)次]均显著低于sham组[(44.94±14.49)s、(32.77±6.22)次],而ESPS+HBO组[(35.49±13.04)s、(21.50±5.98)次]则显著高于ESPS组(均P<0.05).(2)与sham组开臂停留时间[(54.47±23.23)s]、开臂停留时间百分比[(17.91±8.11)%]和进入开臂次数[(10.54±3.85)次]比较,ESPS组各指标[(26.18±8.56)s]、[(7.23±4.24)%]和[(3.10±1.96)次]均显著降低,而ESPS+HBO组各指标[(40.77±16.66)s]、[(13.66±8.81)%]和[(6.40±1.71)次]均显著高于ESPS组(均P<0.05).(3)ESPS组环境诱发僵直时间[(183.21±25.83)s]和声音诱发僵直时间[(202.03±47.79)s]均显著高于sham组和ESPS+HBO组(均P<0.05).(4)ESPS组海马Nrf2(0.23±0.08)和HO-1(0.84±0.13)的蛋白相对表达水平均显著低于sham组和ESPS+HBO组(均P<0.05).(5)sham组与HBO组在上述行为和分子表达指标之间的差异均无统计学意义(均P>0.05).结论高压氧早期干预可能通过调节海马的抗氧化系统Nrf2/HO-1的表达水平改善PTSDObjective To investigate the effects of early intervention of hyperbaric oxygen(HBO)on the behavioral changes and the levels of transcription factor NF-E2-related factor 2(Nrf2)and heme oxygenase-1(heme oxygenase-1,HO-1)in the hippocampusin of post-traumatic stress disorder(PTSD)model rats.Methods A total of 32 male Sprague-Dawley rats were randomly divided into four groups with 8 in each group:sham group,HBO group,ESPS group and ESPS+HBO group.The rats in ESPS group and ESPs+HBO group were exposed to single prolonged stress for the establishment of PTSD models.The other two groups were placed in the same experimental environment but did not receive ESPS at the same time.24 h later,rats placed in hyperbaric oxygen chamber and exposed to 100%oxygen at 2.5 atmospheric absolute or atmospheric air for 1 h each day for 5 consecutive days.7 days after the end of the intervention,rats were experienced open field test,elevated plus maze test and fear conditioning test,then sacrificed and the levels of Nrf2 and HO-1 in the hippocampus were determined by Western blot.Results(1)There was no significant difference in the total distance between the each group(P>0.05).The exploration time[(20.52±9.25)s]and the number of times(15.22±4.38)in the ESPS group were significantly lower than those in the sham group[(44.94±14.49)s and(32.77±6.22)],while the ESPS+HBO group[(35.49±13.04)s and(21.50±5.98)]were significantly higher than those in the ESPS group(P<0.05).(2)Compared with time spent in open arm[(54.47±23.23)s],the percentage of open arm stay time(17.91±8.11)%and the number of open arm entry(10.54±3.85)of sham group,the time spent in open arm[(26.18±8.56)s],the percentage of open arm stay time(7.23±4.24)%and the number of open arm entry(3.10±1.96)were significantly reduced in ESPS group.In ESPS+HBO group,the time spent in open arm[(40.77±16.66)s],the percentage of open arm stay time(13.66±8.81)%and the number of open arm entry(6.40±1.71)were significantly higher than those in ESPs group(P<0.05).(3)The freezing ti

关 键 词：高压氧 创伤后应激障碍 核因子E2相关因子2 血红素加氧酶1 

分 类 号：R749.5[医药卫生—神经病学与精神病学] R-332[医药卫生—临床医学]