CAJ | 학술논문

背景:内源性阿片肽-阿片受体系统的改变是阿片类药物成瘾的一个重要机制.在离体条件下,给予μ阿片受体拮抗剂或激动剂可以调节阿片受体水平.但不同的实验结果差别很大.目的:用光学放射自显影术对吗啡依赖与戒断大鼠脑组织μ阿片受体进行定位和定量研究.设计:完全随机分组实验研究.地点和对象:实验在第二军医大学长征医院麻醉科完成,对象为雄性SD大鼠30只,体质量180～220 g,由第二军医大学动物实验中心提供.干预:30只SD大鼠随机分为吗啡依赖组、吗啡戒断组和生理盐水对照组,每组10只.依赖组和戒断组大鼠以腹腔注射吗啡的方法建立吗啡依赖模型,戒断组在成瘾后腹腔注射纳洛酮5 mg/kg诱导戒断24 h,对照组注射生理盐水.主要观察指标:大鼠不同脑区μ阿片受体特异性结合密度.结果:依赖组大鼠与对照组大鼠相比,额叶皮质、海马、纹状体、丘脑、下丘脑的μ受体特异性结合密度发生非常显著下降(t=11.54,17.82,15.80,8.35,13.78,P＜0.01),下降幅度分别为22%,49%,21%,28%,39%;戒断组大鼠与吗啡依赖组比较,额叶皮质、海马、纹状体、丘脑、下丘脑的μ受体特异性结合密度发生了显著的上调(t=3.72,7.77,5.84,3.06,11.24,P＜0.01),上调幅度分别为10%,38%,12%,13%,58%.但除下丘脑外(t=1.64,P＞0.05),其余脑区的μ受体特异性结合密度仍非常显著地低于正常水平(t=6.76,11.73,10.19,5.46,P＜0.01).结论:大鼠不同脑区在吗啡成瘾过程中μ阿片受体出现明显下调,予纳洛酮催促戒断,μ阿片受体较依赖组大鼠有显著回升,但仍显著低于正常组水平,这可能是阿片类依赖和戒断的重要神经生物学机制之一.
배경:내원성아편태-아편수체계통적개변시아편류약물성은적일개중요궤제.재리체조건하,급여μ아편수체길항제혹격동제가이조절아편수체수평.단불동적실험결과차별흔대.목적:용광학방사자현영술대마배의뢰여계단대서뇌조직μ아편수체진행정위화정량연구.설계:완전수궤분조실험연구.지점화대상:실험재제이군의대학장정의원마취과완성,대상위웅성SD대서30지,체질량180～220 g,유제이군의대학동물실험중심제공.간예:30지SD대서수궤분위마배의뢰조、마배계단조화생리염수대조조,매조10지.의뢰조화계단조대서이복강주사마배적방법건립마배의뢰모형,계단조재성은후복강주사납락동5 mg/kg유도계단24 h,대조조주사생리염수.주요관찰지표:대서불동뇌구μ아편수체특이성결합밀도.결과:의뢰조대서여대조조대서상비,액협피질、해마、문상체、구뇌、하구뇌적μ수체특이성결합밀도발생비상현저하강(t=11.54,17.82,15.80,8.35,13.78,P＜0.01),하강폭도분별위22%,49%,21%,28%,39%;계단조대서여마배의뢰조비교,액협피질、해마、문상체、구뇌、하구뇌적μ수체특이성결합밀도발생료현저적상조(t=3.72,7.77,5.84,3.06,11.24,P＜0.01),상조폭도분별위10%,38%,12%,13%,58%.단제하구뇌외(t=1.64,P＞0.05),기여뇌구적μ수체특이성결합밀도잉비상현저지저우정상수평(t=6.76,11.73,10.19,5.46,P＜0.01).결론:대서불동뇌구재마배성은과정중μ아편수체출현명현하조,여납락동최촉계단,μ아편수체교의뢰조대서유현저회승,단잉현저저우정상조수평,저가능시아편류의뢰화계단적중요신경생물학궤제지일.
BACKGROUND: The alteration of endogenous opioid peptide system is one of the important mechanisms for opioid dependence, μ opioid receptor antagonist or activator can regulate opioid receptor in vitro, but the results from the animal experiment vary greatly.OBJECTIVE: To study the locahzation and quantitative changes of μ-opioid receptor in the brain tissues of morphine-dependent and abstinent rats.DESIGN: A completely randomized controlled experimental study.SETTING and MATERIALS: The experiment was conducted in the Depurtment of Anaesthesiology, Changzheng Hospital, Second Military Medical University using 30 male SD rats provided by the Experimental Animal Center, Second Military Medical University.INTERVENTIONS: Thirty SD rats were divided randomly into 3 groups( n =10) . Intraperitoneal injection with morphine was given to the rats in morphine-dependent group and abstinent group to produce morphine - dependent models, and 3 hours after the model establishment, the rats in the abstinent group were injected with naloxone(5 mg/kg) to induce the withdrawal syndromes. The rats in the control group received only injection with saline. All rats were sacrificed by decapitation 24 hours after the last injection of morphine, and the coronal sections of discrete brain regions(namely the frontal cortex, hippocampus, striatum, thalamus, and hypothalamus) were prepared.MAIN OUTCOME MEASURES: The localization and density of μ-opioid receptor in the specified brain regions of rats in all the 3 groups were measured by autoradiography.RESULTS: In morphine dependent group, the density ofμ-opioid receptor in the frontal cortex, hippocampus, striatum, thalamus, and hypothalamus were significantly lowered by 22%, 49%, 21% and 28%, respectively( t = 11.54,17.82, 15.80, 8.35, 13.78, respectively, P ＜ 0. 01) in comparison with the control group. In morphine abstinent group, the densities of μ opioid receptor in those brain regions were significantly higher by 10%, 38%, 12%, 13%, and 58% respectively(t =3.72, 7.77, 5.84, 3.06, 11.24, respectively, P ＜0.01 ) than those in dependent group, but remained lower in then frontal cortex, hippocampus, striatum, thalamus that those in the control group( t = 6. 76,11.73, 10. 19, 5.46, respectively, P ＜ 0.01 ) with the exception of that in the hypothalamus( t = 1.64, P ＞ 0.05).CONCLUSION: Morphine dependence can lower the level of μ-opioid receptor in rat brain, which is difficult to correct through short-term morphine abstinence by naloxone and can be one of the neurobiological mechanisms of opioid dependence and abstinence.