Orexin-A介导histamine能神经系统促进氯胺酮麻醉觉醒

Orexin-A Facilitates Emergence from Katemine Anesthesia through Histaminergic System

目的:探索氯胺酮麻醉下,Orexin神经信号是否激活结节乳头体核(Tuberomammillary Nucleus,TMN)促进大鼠氯胺酮麻醉觉醒。方法:成年雄性SD大鼠(体重230-280 g),在10%水合氯醛麻醉下(1 ml/kg,i.p.)进行以下实验:1TMN核团埋置微注射外套管,回笼单独饲养7天后,大鼠随机分为三组,分别为对照组(NS)、orexin-A组与orexin-B组。TMN核团分别双侧微注射NS(0.3μL)、orexin-A(100 pmol/0.3μL)及orexin-B(100 pmol/0.3μL)观察氯胺酮麻醉下(100 mg/kg,腹腔注射)大鼠诱导时间与觉醒时间;2上述实验7天后,大鼠随机分为三组,分别为溶剂DMSO组、SB334867组与TCS-OX2-29组,TMN核团分别双侧微注射DMSO(0.3μL)、orexin 1型受体(the orexin type 1 receptor,OX1R)的拮抗剂SB334867(20μg/0.3μL)和orexin 2型受体(the orexin type 2 receptor,OX2R)的拮抗剂TCS-OX2-29(20μg/0.3μL)观察氯胺酮麻醉下大鼠诱导时间与觉醒时间。结果:1各组大鼠的诱导时间无统计学差异。2在TMN核团微注射orexin-A与对照组相比明显缩短了大鼠的觉醒时间(43.17±6.31 min vs51.17±4.45 min,P<0.05),而微注射orexin-B与对照组相比并没有明显影响大鼠的觉醒时间(50.33±3.50 min vs 51.17±4.45min,P>0.05)。3TMN核团微注射OX1R拮抗剂SB334867较溶剂DMSO组延长了麻醉觉醒时间(60.83±8.84 min vs 49.00±5.73 min,P<0.05),OX2R拮抗剂TCS-OX2-29与溶剂DMSO组相比并没有明显影响大鼠的觉醒时间(50.83±4.79 min vs 49.00±5.73 min,P>0.05)。结论:本研究实验证据证实在氯胺酮麻醉下,orexin神经信号可能通过激活TMN区组胺能神经系统促进麻醉向觉醒的转换。

Objective： The aim of this study was to test whether activation of orexin signal in Tuberomammillary Nucleus （TMN） can facilitate emergence from katemine anesthesia or not. Methods： Adult male SD rats （body weight 230-280 g） were anesthetized by 10% chloral hydrate （1 ml/kg, ip） to do the following work. （1）Guide cannulas for microinjection to the TMN were embedded. Then the rats were fed in separate cage. Seven days later, rats were randomly divided into three groups. And then orexin-A （100 μmol/0.3 μL）, orexin-B （100 μmol/0.3 μL） and and their solvent NS （0.3 μL） were microinjected into TMN respectively to observe the induction time and awakening time in rats. （2）The same operation as step 1, Seven days later, rats were grouped randomly. And then the OX1R antagonist SB334867 （20 μL/0.3 μL）, OX2R antagonist TCS-OX2-29 and their solvent DMSO （0.3 μL） were microinjected into TMN respectively to observe the time of induction and awakening in rats. Results： （1）No statistical difference of induction time was found in each group. （2）The rats which injected orexin-A （100 pmol/0.3μL） recovered much faster from ketamine anesthesia （100 mg/kg, ip） than controlled group （injected NS 0.3 μL） （43.17± 6.31 min vs 51.17± 4.45 min,P〈0.05）.There was no significant difference on the emergence from ketamine anesthesia between the rats received orexin-B and controlled rats （50.33 ±3.50 min vs 51.17± 4.45 min, P〉0.05）. （3）The injection of OX1R antagonist SB334867 （20 μL/0.3 μL） to TMN could prolong the emergence time from ketamine anesthesia compared to the solvent DMSO （0.3μL） group （60.83± 8.84 min vs 49.00±5.73 min, P〈0.05）. The injection of OX2R antagonist TCS-OX2-29 did not significantly affect the rat emergence time （50.83± 4.79 rain vs 49.00± 5.73 min, P〉0.05）. Conclusion： Orexin-A Can facilitates emergence awakening from ketamine anesthesia through histaminergic system in TMN.