【原】食欲肽通過興奮大鼠中腦腹側(cè)被蓋區(qū)多巴胺能神經(jīng)元參與異氟醚麻醉

罌粟花anesthGH 2021-07-21

展開全文

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Orexin activated emergence from isoflurane anaesthesia involves excitation of ventral tegmental area dopaminergic neurones in rats

背景與目的

食欲肽可通過多種神經(jīng)通路促進(jìn)全身麻醉作用的產(chǎn)生。腹側(cè)被蓋區(qū)(VTA)的多巴胺能神經(jīng)元參與麻醉后的行為覺醒。本研究旨在探討全身麻醉作用出現(xiàn)過程中，食欲肽能神經(jīng)元對(duì)多巴胺能VTA神經(jīng)元的調(diào)節(jié)作用。

方法

將食欲肽微量注射到VTA中，以檢測(cè)異氟醚麻醉誘導(dǎo)、產(chǎn)生和維持的效果。免疫熒光法鑒定VTA中的食欲肽受體和多巴胺能神經(jīng)元。采用光遺傳學(xué)技術(shù)校準(zhǔn)VTA中食欲肽能神經(jīng)元末端以檢測(cè)Hcrt^cre大鼠麻醉過程中內(nèi)源性食欲肽介導(dǎo)的多巴胺能神經(jīng)元調(diào)節(jié)作用。

結(jié) 果

在VTA中注射食欲肽A(100 pmol)可縮短麻醉出現(xiàn)時(shí)間(從949 [118]s降至727 [101]s;P=0.0058)，并降低了異氟醚麻醉期間腦電圖的發(fā)作-抑制率(BSR) (26.6 [10.2]% vs 44.3 [6.8]%;P=0.0027)。表達(dá)食欲肽-1受體或食欲肽-2受體的多巴胺能神經(jīng)元的百分比分別為73.4(5.0)%和74.4(62.4)%。VTA中食欲肽能神經(jīng)元投影的光遺傳學(xué)活化作用減少了BSR(從40.5[2.7]%降至22.4 [11.8]%;P=0.0019)，促進(jìn)了麻醉作用的產(chǎn)生(915 [89]vs 685 [68] s;P=0.0026)，而光學(xué)抑制延長(zhǎng)了覺醒時(shí)間(從941[92]到1279 [250]s;P = 0.011)。應(yīng)用食欲肽A后，VTA中多巴胺能神經(jīng)元的放電頻率增加(對(duì)照組387 [78]%，P=0.005)。

結(jié) 論

食欲肽通過激活VTA中的多巴胺能神經(jīng)元，促進(jìn)異氟醚麻醉作用的產(chǎn)生。

原始文獻(xiàn)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 Hcrt^crerats.

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. 金屬質(zhì)感分割線