右美托咪啶复合舒芬太尼对大鼠镇静、呼吸抑制影响及作用机制研究  

Effects and mechanism of dexmedetomidine combined with sufentanil on sedation and respiratory depression in rats

作　　者：王燕[1] 柳璐 孙志鹏 陈建妍 WANG Yan;LIU Lu;SUN Zhi-peng;CHEN Jian-yan(Department of Anesthesiology,Wuhan Children’s Hospital,Wuhan Maternal and Child Health Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430016,China)

机构地区：[1]华中科技大学同济医学院附属武汉儿童医院(武汉市妇幼保健院)麻醉科,武汉430016

出　　处：《药物分析杂志》2021年第6期962-969,共8页Chinese Journal of Pharmaceutical Analysis

基　　金：湖北省自然科学基金计划项目(2018CFC856)。

摘　　要：目的:用动物实验,分析右美托咪啶复合舒芬太尼对大鼠镇静、呼吸抑制的影响,并探讨药物具体作用机制。方法:收集80只健康SD雄性大鼠,翻正反射实验分组为实验组1、实验组2、实验组3,镇静实验分组为实验组4、实验组5、实验组6,肺功能实验、及磷脂酰肌醇3激酶(PI3K)、蛋白激酶B(Akt)、磷酸化Akt(p-Akt)蛋白相对表达量检测分组为对照组、实验组7、实验组8、实验组9,液相色谱-串联质谱(LCMS/MS)实验分组为实验组10、实验组11、实验组12。实验组1、4、7、10以20.0μg·kg^(-1)舒芬太尼尾静脉注射,实验组2、5、8、11以25.2μg·kg^(-1)右美托咪啶尾静脉注射,实验组3、6、9、12以20.0μg·kg^(-1)舒芬太尼联合25.2μg·kg^(-1)右美托咪啶尾静脉注射,对照组以等量生理盐水尾静脉注射。结果:翻正反射实验中,与实验组1比较,实验组2诱导时间增加,实验组3诱导时间减少(P<0.05);与实验组2比较,实验组3诱导时间减少(P<0.05);与实验组1比较,实验组2、实验组3持续时间延长(P<0.05);与实验组2比较,实验组3持续时间延长(P<0.05)。给药30、40 min时,实验组4、实验组5、实验组6镇静效果评分升高,但实验组6较实验组4、实验组5低。与实验组7比较,实验组8、实验组9 RF、TV、MV变化率降低,呼吸抑制发生时间较慢,持续时间延长,PI3K、p-Akt、p-Akt/Akt蛋白相对表达量升高(P<0.05);与实验组8比较,实验组9呼吸抑制持续时间延长,PI3K、p-Akt、p-Akt/Akt蛋白相对表达量升高(P<0.05)。给药5、15 min时,与实验组10比较,实验组12舒芬太尼血浆、脑组织浓度及Kp值降低(P<0.05)。给药5、15 min时,与实验组11比较,实验组12右美托咪啶血浆浓度降低,脑组织浓度、Kp值升高(P<0.05)。结论:右美托咪啶复合舒芬太尼可延长大鼠镇静时间、呼吸抑制持续时间,机制可能与激活PI3K/Akt通路有关。Objective:To study the effects of dexmedetomidine and sufentanil on the sedation and respiratory inhibition of rats and to explore the specific mechanism of the drug using animal experiment.Methods:Eightyhealthy male SD rats were divided into experimental group 1,2 and 3,sedation group 4,5 and 6.Lung function test and relative expression of phosphatidylinositol 3 kinase(PI3 K),protein kinase B(Akt)and phosphorylated Akt(p-Akt)protein were detected and divided into control group,experimental group 7,experimental group 8 and experimental group 9.Liquid chromatography tandem mass spectrometry(LCMS/MS)experiments was divided into experimental group 10,experimental group 11 and experimental group 12.Sufentanil(20.0μg·kg^(-1))was injected into the tail vein of experimental group 1,4,7 and 10,dexmedetomidine(25.2μg·kg^(-1))was injected in experimental group 2,5,8 and 11,and 20.0μg·kg^(-1)sufentanil combined with 25.2μg·kg^(-1)dexmedetomidine were injected in experimental group 3,6,9 and 12.The control group was injected with equal amount of physiological saline.Results:In the righting reflex experiment,compared with group 1,the induction time of group 2 was increased,while that of group 3 was decreased(P<0.05).Compared with group 2,the induction time of group 3 was decreased(P<0.05).Compared with experimental group 1,the duration of experimental group 2 and group 3 was prolonged(P<0.05).Compared with group 2,the duration of group 3 was prolonged(P<0.05).At 30 min and 40 min after administration,the sedative effect scores of experimental group 4,5 and 6 increased,but the sedative effect score of experimental group 6 was lower than that of experimental group 4 and 5.Compared with experimental group 7,the change rate of RF,TV and MV in experimental group 8 and 9 decreased,the occurrence time of respiratory depression was slower,the duration of respiratory depression was prolonged,and the relative expression of PI3 K,p-Akt and p-Akt/Akt protein was increased(P<0.05).Compared with experimental group 8,the duration of

关 键 词：右美托咪啶 舒芬太尼 镇静 呼吸抑制 作用机制 

分 类 号：R917[医药卫生—药物分析学]