吗啡耐受猴脑内葡萄糖代谢的显像研究

Study on cerebral glucose metabolism for morphine tolerance in monkey

目的:研究猴脑内对吗啡耐受敏感的神经定位,探讨吗啡耐受的可能机制。方法:选择健康猴5只,采用PHILIPS CPET Plus扫描仪行PET扫描,观察正常脑内各区的葡萄糖代谢率(CMRGlu)。每天肌肉注射吗啡10mg/kg,连续1周,使猴对吗啡产生耐受,然后再次行PET扫描,观察吗啡耐受后脑内各区的CMRGlu。比较两次扫描脑内各区CMRGlu的变化情况。在两次扫描的横断面上分别划出8个断面,每一断面划出全脑范围的感兴趣区(ROI),并分别划出额叶、颞叶、枕叶、顶叶、丘脑、基底核、纹状体、扣带回、桥脑、海马和小脑等脑区ROI,计算各ROI内平均每像素点的计数。结果:(1)吗啡耐受前全脑内CMRGlu计数2119±114,耐受后计数为1721±105,显著降低(P<0.05)。(2)与吗啡耐受前比较,耐受后扣带回、桥脑和基底核CMRGlu计数降低(P<0.01),分别由3307±157、3114±104和3038±138降至2029±108、2176±136和2126±115,降低38.6%、30.1%和30.0%,但其他脑功能区无显著变化。结论:长期使用吗啡对猴脑葡萄糖代谢具有一定的抑制作用,尤以扣带回、桥脑和基底核等局部CMRGlu降低最为显著,提示扣带回、桥脑和基底核对吗啡类药物更为敏感,可能是吗啡类药物在脑内作用的主要靶区。

Objective To study the targets of morphine tolerance in monkey, and to probe the mechanism of morphine tolerance. Methods 5 healthy monkeys were scanned by PHILIPS CPET Plus scanner to observe normal glucose metabolism of various regional brain areas and then were injected 10 mg/kg morphine once a day （lasting one week） to establish morphine tolerance model. After one week morphin injection, these monkeys were scanned to observe glucose metabolism of various regional brain areas again. Results （1）Whole brain glucose metabolism count was 2 119 ± 114, and decreased to 1 721 ± 105 after one week morphin injection （P〈 0.05）. （2）Compared with normal monkeys, regional glucose metabolism count in cingulate gyms, pans and basal ganglia of morphin tolerance monkeys decreased significantly （P〈 0.01） from 3 307 ± 157, 3 114 ± 104 and 3 038 ± 138 to 2 029 ± 108, 2 176 ± 136 and 2 126 ± 115. Decrease rate was 38.6%, 30.1% and 30.0% respectively. Glucose metabolism count of other regional brain areas remained normal after morphine tolerance. Conclusions Long-time usage of morphine may inhibit glucose metabolism of monkey＇s various brain areas except cingulate gyms, pans and basal ganglia, which indicates that cingulate gyms, pons and basal ganglia are more sensitive to opioid drugs and may be the main targets of opioid drugs.