大鼠腹侧被盖区多巴胺能神经元介导食欲素促进全麻后觉醒效应  

Dopaminergic neurons in ventral tegmental area mediate the arousal-promotive effect of orexin following general anesthesia in rats

作　　者：李健楠 李慧明 张欣欣 董海龙 Li Jiannan;Li Huiming;Zhang Xinxin;Dong Hailong(Department of Anesthesia and Peri-operative Medicine,Xijing Hospital,Air Force military Medical University,Xi'an 710032,China)

机构地区：[1]空军军医大学西京医院麻醉与围术期医学科,西安710032

出　　处：《神经解剖学杂志》2021年第1期1-7,共7页Chinese Journal of Neuroanatomy

基　　金：科技部国家重点研发项目(2017YFC1308402)。

摘　　要：目的:研究大鼠腹侧被盖区(VTA)多巴胺能神经元是否介导食欲素(orexin)的促进全麻后觉醒效应。方法:将兴奋性光遗传病毒注射至Hcrt-cre大鼠的orexin阳性神经元所在的下丘脑外侧穹隆周区(PeFLH),同时在VTA区注射抑制性化学遗传病毒及带有酪氨酸羟化酶(TH)-cre的混合病毒抑制多巴胺能神经元,并在VTA区植入光纤。观察通过化学遗传抑制VTA区多巴胺能神经元后,光遗传兴奋VTA区的orexin阳性神经投射终末是否仍能引起促进异氟醚麻醉后觉醒的效应。结果:与对照组相比,用化学遗传技术预先抑制VTA区多巴胺能神经元,阻断了光遗传兴奋VTA区orexin阳性神经投射终末所产生的缩短大鼠1.4%异氟醚麻醉后觉醒时间的作用;并阻断了光遗传兴奋VTA区orexin阳性神经投射终末所产生的降低大鼠1.4%异氟醚麻醉中脑电图爆发抑制率(BSR)效应。用Fos染色法验证了化学遗传法抑制多巴胺能神经元的可靠性。结论:抑制VTA区的多巴胺能神经元能够阻断兴奋大鼠VTA区orexin阳性神经末梢所产生的促进大鼠异氟醚后觉醒的效应,提示VTA区的多巴胺神经神经元介导了orexin调控VTA区产生的促进觉醒效应。Objective:To investigate whether the dopaminergic neurons in the ventral tegmental area(VTA)in rats mediate the arousal effect of orexin following general anesthesia.Methods:Excitatory optogenetic virus was injected into the lateral perifornical area of hypothalamus(Pe FLH)where orexin positive neurons located in Hcrt-cre rats.At the same time,inhibitory chemogenetic virus mixed with tyrosine hydroxylase-cre(TH-cre,to specifically label dopaminergic neurons)virus was injected into VTA,and the optical fiber was implanted in the VTA.We investigated whether the optogenetically excited orexin positive nerve terminals in the VTA could still promote arousal during isoflurane anesthesia under the condition of chemogenetic inhibition of dopaminergic neurons in the VTA.Results:Compared with the control group,pre-inhibition of the VTA dopaminergic neurons in 1.4%isoflurane anesthesia in rats blocked the effect of shortening the emergence time and blocked the effect of reducing burst-suppression-ratio(BSR)induced by optogenetic excitation of orexin positive terminals in the VTA.The reliability of chemogenetic method of inhibiting dopaminergic neurons was proved by Fos staining.Conclusion:Inhibition of dopaminergic neurons in the VTA can block the arousal-promoting effect produced by stimulating orexin positive terminals in the VTA,indicating dopaminergic neurons mediate the arousal-promoting effect of orexin in regulating the VTA of rats.

关 键 词：觉醒 食欲素 腹侧被盖区 多巴胺能神经元 光遗传学 化学遗传学 大鼠 

分 类 号：R614[医药卫生—麻醉学]