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Orexin activated emergence from isoflurane anaesthesia involves excitation of ventral tegmental area dopaminergic neurones in rats
背景与目的
食欲肽可通过多种神经通路促进全身麻醉作用的产生。腹侧被盖区(VTA)的多巴胺能神经元参与麻醉后的行为觉醒。本研究旨在探讨全身麻醉作用出现过程中，食欲肽能神经元对多巴胺能VTA神经元的调节作用。
方 法
将食欲肽微量注射到VTA中，以检测异氟醚麻醉诱导、产生和维持的效果。免疫荧光法鉴定VTA中的食欲肽受体和多巴胺能神经元。采用光遗传学技术校准VTA中食欲肽能神经元末端以检测Hcrtcre大鼠麻醉过程中内源性食欲肽介导的多巴胺能神经元调节作用。
结 果
在VTA中注射食欲肽A(100 pmol)可缩短麻醉出现时间(从949 [118]s降至727 [101]s;P=0.0058)，并降低了异氟醚麻醉期间脑电图的发作-抑制率(BSR) (26.6 [10.2]% vs 44.3 [6.8]%;P=0.0027)。表达食欲肽-1受体或食欲肽-2受体的多巴胺能神经元的百分比分别为73.4(5.0)%和74.4(62.4)%。VTA中食欲肽能神经元投影的光遗传学活化作用减少了BSR(从40.5[2.7]%降至22.4 [11.8]%;P=0.0019)，促进了麻醉作用的产生(915 [89]vs 685 [68] s;P=0.0026)，而光学抑制延长了觉醒时间(从941[92]到1279 [250]s;P = 0.011)。应用食欲肽A后，VTA中多巴胺能神经元的放电频率增加(对照组387 [78]%，P=0.005)。
结 论
食欲肽通过激活VTA中的多巴胺能神经元，促进异氟醚麻醉作用的产生。
原始文献摘要
Li J, Li H, Wang D, et al. Orexin activated emergence from isoflurane anaesthesia involves excitation of ventral tegmental area dopaminergic neurones in rats[J]. Br J Anaesth,2019,123(4):497-505.
Background: Orexin can facilitate emergence after general anaesthesia via multiple neural pathways. Dopaminergic neurones in the ventral tegmental area (VTA) participate in behavioural arousal from anaesthesia. We investigated the regulation of dopaminergic VTA neurones by orexinergic neurones during emergence from general anaesthesia.
Methods: Orexins were microinjected into the VTA to determine the effects on isoflurane anaesthesia induction, emergence, and maintenance. Orexin receptors and dopaminergic neurones in the VTA were identifified using immunofluorescence. Orexinergic terminals in the VTA were optogenetically regulated to detect the endogenous orexinmediated regulation of dopaminergic neurones during anaesthesia in Hcrtcre rats.
Results: Injection of orexin-A (100 pmol) into the VTA reduced emergence time [from 949 (118) to 727 (101) s; P=0.0058] and reduced the electroencephalographic burst-suppression ratio (BSR) (26.6 [10.2]% vs 44.3 [6.8]%; P=0.0027) during isoflurane anaesthesia. The percentage of dopaminergic neurones that expressed either orexin-1 receptor or orexin-2 receptor was 73.4 (5.0)% and 74.4 (62.4)%, respectively. Optogenetic activation of orexinergic projections to the VTA reduced the BSR (from 40.5 [2.7]% to 22.4 [11.8]%; P=0.0019) and facilitated emergence (915 [89] vs 685 [68] s; P=0.0026), whereas optical inhibition prolonged the time to wakefulness (from 941 [92] to 1279 [250] s; P=0.011). Dopaminergic neurones in the VTA showed increased firing frequency (387 [78]% of control, P=0.005) after bath application of orexin-A.
Conclusions: Orexin promotes emergence from isoflurane anaesthesia through activation of dopaminergic neurones in the VTA.
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贵州医科大学高鸿教授课题组
翻译：冯玉蓉 编辑：何幼芹 审校：王贵龙
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