7-羟乙基白杨素对低压低氧大鼠认知功能的保护作用及机制研究  

Protective Effects and mechanism of 7-HEC against hypobaric hypoxia-induced cognitive impairments in rats

作　　者：景临林 杨颖 邵瑾 赵彤 贾正平 马慧萍 JING Lin-lin;YANG Ying;SHAO Jin;ZHAO Tong;JIA Zheng-ping;MA Hui-ping(Department of Pharmacy,The 940 th Hospital of Joint Logistics Support force of PLA,The Lab of PLA for High Altitude Medicine,Gansu Lanzhou 730050,China)

机构地区：[1]联勤保障部队第九四〇医院药剂科,全军高原医学实验室,甘肃兰州730050

出　　处：《中国医院药学杂志》2020年第15期1622-1626,共5页Chinese Journal of Hospital Pharmacy

基　　金：国家自然科学基金项目(81872796,81202458,81571847);军队后勤科研计划(CWH17J010);甘肃省自然科学基金(18JR3RA408,1308RJYA061,145RJZA089);中国博士后科学基金(2012M521926)。

摘　　要：目的:研究7-羟乙基白杨素(7-HEC)对低压低氧致大鼠认知功能损伤的保护作用及其机制。方法:将48只雄性大鼠随机分为正常对照组、缺氧模型组、白杨素组和7-HEC组,连续灌胃给药5 d,其中舱外2 d,然后将大鼠置于模拟海拔8000 m环境停留3 d,期间每天给药一次。八臂迷宫检测大鼠空间学习记忆能力,HE染色观察脑组织海马区病理改变,检测海马组织中H2O2、MDA和抗氧化酶的活性变化,ELISA法检测炎性因子IL-6、IL-1β、TNF-α的水平,蛋白印迹法检测Bcl-2、Bax和caspase-3蛋白的表达情况。结果:低压低氧导致大鼠海马组织损伤明显,参考记忆错误(RME)、工作记忆错误(WME)、总错误次数(TE)和总时间(TT)显著升高,海马组织中H2O2、MDA含量和炎性因子水平显著增加,抗氧化酶活性显著减低,Bax和caspase-3蛋白表达增加,Bcl-2蛋白表达降低。经7-HEC预处理后能够显著降低WME、RME、TE和TT,降低大鼠海马组织中H2O2、MDA含量和炎性因子水平,提高抗氧化酶活性,降低Bax和caspase-3蛋白表达,显著提高Bcl-2蛋白的表达。结论:7-HEC能够减轻低压低氧诱导的认知功能损伤,作用机制可能与清除自由基,提高抗氧化酶活性,降低机体氧化应激,抑制炎性反应和细胞凋亡有关。OBJECTIVE To evaluate the protective effect and mechanism of 7-HEC against hypobaric hypoxia-induced cognitive impairments in rats.METHODS 48 male Wistar rats were randomLy divided into normal control group,hypoxia model group,acetazolamide group and 7-HEC group.Rats were supplemented with drugs orally for two days.After the third day of drug administration,rats were exposed to a 8000 m altitude for 3 days and were given drug daily during the period of exposure.Spatial memory was assessed by the 8-arm radial maze test.The pathological changes of hippocampus were assessed by hematoxylin-eosin(HE)staining.The H2O2,MDA level and antioxidant enzymes activity in the hippocampus tissue was monitored by kits.The contents of IL-6、IL-1βand TNF-αwere evaluated by ELISA.The expression levels of Bcl-2,Bax and caspase-3 were determined by Western blotting.RESULTS Compared with control group,hypobaric hypoxia exposure induced memory impairment,as evidence by the increased values obtained for reference memory error(RME),working memory error(WME),total number of errors(TE)and total time(TT),concomitantly with elevation of the level of H2O2,MDA and inflammatory cytokines and decrease in the activity of antioxidant enzymes.HH exposure also signi?cantly up-regulated the expression levels of Bax,caspase-3 and down-regulated the expression of Bcl-2.Compared with hypoxia groups,prior administration of 7-HEC ameliorated memory impairment with lower RME,WME,TE and TT,decreased the level of H2O2,MDA and inflammatory cytokines and increased antioxidant enzymes activity.7-HEC could inhibit the expression of Bax,caspase-3,while unregulating Bcl-2 expression.CONCLUSION 7-HEC can reduce the cognitive impairment induced by hypobaric hypoxia,and the mechanism may be related to scavenging free radicals,increasing the activity of antioxidant enzymes,decreasing oxidative stress,inhibiting inflammatory response and apoptosis.

关 键 词：7-羟乙基白杨素 低压低氧 海马组织 氧化应激 炎症反应 凋亡 

分 类 号：R285[医药卫生—中药学]