摘要
目的研究异氟醚后处理对缺血缺氧性脑损伤新生大鼠远期认知功能及脑组织胰岛素样生长因子-1(IGF-1)、脑源性神经营养因子(BDNF)、神经生长因子(NGF)的影响,探讨异氟醚后处理对新生大鼠缺血缺氧脑损伤的保护作用及作用机制。方法 125只新生7 d的SD大鼠,随机分为假手术组、模型组(HIBD组)、1%异氟醚组(Iso1组)、2%异氟醚组(Iso2组)、3%异氟醚组(Iso3组),每组25只,各组大鼠均麻醉后切开颈部皮肤,假手术组找到左侧颈总动脉不结扎,其他各组均结扎。除假手术组,其他各组大鼠均持续吸入8%O2和92%N2的低氧气体2 h,制备新生大鼠缺血缺氧脑损伤模型。手术结束后,Iso1、Iso2、Iso3组分别于半密闭容器中吸入1%、2%、3%异氟醚,假手术组与模型组吸入30%O2及70%N2混合气体,吸入时间均为1 h,造模后第20天开始对各组大鼠进行Morris水迷宫定位航行试验,记录各大鼠的逃避潜伏期、总路程及空间探索力,连续5 d,对第5天的试验数据作为认知功能结果进行对比;水迷宫试验结束后,处死大鼠,取海马组织,镜下观察大鼠海马CA3区左、右侧组织神经元密度;RT-PCR法检测大鼠海马体中IGF-1、BDNF、NGF的mRNA表达情况。结果与假手术组对比,HIBD组大鼠逃避潜伏期、总路程显著延长,空间探索力下降,差异均有统计学意义(P<0.05)。与HIBD组对比,Iso1、Iso2、Iso3组逃避潜伏期、总路程显著下降,空间探索力提高,Iso2、Iso3组变化更加显著,差异有统计学意义(P<0.05)。HIBD组大鼠海马体组织中神经密度下降,Iso1、Iso2、Iso3组较HIBD组有所改善。HIBD组大鼠海马体中IGF-1、BDNF、NGF表达较假手术组升高,Iso1、Iso2、Iso3组海马体中IGF-1、BDNF、NGF表达较HIBD组提高,Iso2、Iso3组变化更加显著,差异有统计学意义(P<0.05)。结论异氟醚后处理对新生大鼠缺血缺氧性脑损伤具有保护作用,可改善大鼠远期认知功能,这种作用可能与调节大鼠脑组织IGF-1、BDNF、NGF的表达,保护神经元相关。
Objective To study the effects of isoflurane postconditioning on long-term cognitive function and brain tissue insulin-like growth factor-1(IGF-1),brain derived neurotrophic factor(BDNF) and nerve growth factor(NGF) in neonatal rats with hypoxic-ischemic brain injury,and explore the protective effect and mechanism of isoflurane postconditioning on neonatal rats with hypoxic-ischemic brain injury.Methods 125 7-days-old SD rats were randomly divided into shamoperated group,model group(HIBD group),1% isoflurane group(Isol),2% isoflurane group(Iso2) and 3% isoflurane group(Iso3),25 rats in each group.After anesthesia,carotid skin was incised in each group.The left common carotid artery was not ligated in sham-operated group.All groups were ligated.Except the sham-operated group,rats in other groups were inhaled 8% O2 and 92% N2 hypoxic gas for 2 hours to prepare the neonatal rat model of ischemic-hypoxic brain injury.After the operation,Isol,Iso2 and Iso3 groups inhaled 1%,2% and 3% isoflurane in semi-closed container,respectively,and sham operation and model group inhaled 30% O2 and 70% N2 mixed gas for 1 hour.Morris water maze positioning navigation test was conducted on the 20th day after the establishment of the model.The escape latency,total distance and duration of each group were recorded.After water maze test,rats were sacrificed and the hippocampal tissue was taken.Neuronal density in left and right hippocampal CA3 area of rats was observed under microscope.The expression of IGF-1,BDNF and NGF in hippocampus was detected by RT-PCR.Results Compared with sham-operated group,the escape latency and total distance of rats in HIBD group were significantly prolonged and their spatial exploratory ability was decreased.Compared with HIBD group,the escape latency and total distance of rats in Isol,Iso2 and Iso3 groups were significantly decreased,and the spatial exploratory ability was improved.The changes of rats in Iso2 and Iso3 groups were more significant with statistical significance(P<0.05).The expression of IGF-1,BDNF and NGF in hippocampus of HIBD group was higher than that of sham-operated group,while the expression of IGF-1,BDNF and NGF in hippocampus of Isol,Iso2 and Iso3 groups was higher than that of HIBD group,and the changes of Iso2 and Iso3 groups were more significant(P<0.05).Conclusions Isoflurane postconditioning had protective effect on neonatal rats with hypoxic-ischemic brain injury and improved long-term cognitive function.This effect might be related to regulating the expression of IGF-1,BDNF and NGF in rat brain tissue and protecting neurons.
作者
康雅琴
朱红
徐继宗
许海
KANG Ya-qin;ZHU Hong;XU Ji-zong;XU Hai(Department of Anesthesiology,Songzi People′s Hospital,Jingzhou,Hubei 434200;Department of Pharmaceutical,the Second People′s Hospital of Yichang,Second Peoples Hospital of China Three Gorges University,Yichang,Hubei 443000;Department of Gynaecology,Hubei University of Traditional Chinese Medicine,Huangjia Lake Hospital,Wuhan,Hubei 430070,China)
出处
《热带医学杂志》
CAS
2020年第9期1136-1139,1151,F0002,共6页
Journal of Tropical Medicine
基金
湖北省自然科学基金(2018CFC808)。
