吗啡依赖及戒断大鼠下丘脑前阿黑皮素原mRNA的变化

目的··:观察大鼠吗啡依赖和戒断状态下脑内前阿黑皮素原 (POMC )mRNA的变化。方法·· :采用腹腔注射法 ,按剂量递增原则建立大鼠吗啡依赖动物模型 ,同时建立生理盐水对照组。吗啡依赖大鼠随机分为依赖组和戒断组。对照组和依赖组动物于末次注射后3h ,戒断组大鼠于末次注射后72h迅速断头处死取脑 ,收集各个脑区组织总RNA标本。以POMC反义RNA探针对得到的RNA标本进行NorthernBlot印迹杂交 ,用电子计算机图像处理系统对所得结果进行分析。结果·· :吗啡依赖大鼠下丘脑POMCmRNA的表达仅为生理盐水对照组的69.56%±s4.7 % ,戒断72h状态下的吗啡依赖大鼠下丘脑POMCmRNA的表达恢复至生理盐水对照组的78.26 %±s5.3 % ;海马、纹状体和垂体POMCmRNA表达均为阴性。结论··:吗啡依赖大鼠下丘脑POMCmRNA的表达较生理盐水对照组有显著下降 ,戒断72h状态下的吗啡依赖大鼠其下丘脑POMCmRNA的表达较依赖组大鼠有显著回升 ,但仍显著低于正常组水平。此结果从分子生物学水平证实阿片类药物依赖机制与其引起内源性阿片肽系统功能变化有关

CHANGESOF POMC mRNA IN HYPOTHALAMUS OF MORPHINE DEPENDENT AND ABSTINENT RATS

Objective: To observe the contents of POMC mRNA in the central nervous system of morphine dependent and abstinent rats. Method: The animal models of morphine dependence were established by intraperitoneal injecting morphine in rats, three times a day, for 9 days. The dose of morphine was added according to an escalating dose schedule. The rats in control group were injected with saline. The rats with morphine dependence were randomly divided into two groups: morphine dependent group and abstinent group. The rats in dependent group and control group were killed 3 hours after the last injection; the rats in abstinent group were killed 72 hours after the last injection of morphine. Then the pituitary, striatum, hypothalamus and hippocampus were collected and the concentration of POMC mRNA of each region was determined by Northern Blot hybridization. The results were analyzed by a computer assisted photograph analysis system. Result: The level of POMC mRNA of morphine dependent group rats was suppressed to 69.56% of that of the control group. In morphine abstinent group the level of POMC mRNA increased to 78.26% of that of the control group compared with the morphine dependent group, but it was still significantly lower than that of the control group.Conclusion:The level of POMC mRNA of morphine dependent group rats was suppressed significantly. In morphine abstinent group the level of POMC mRNA increased compared with that of the morphine dependent group, but it was still lower than that of the control group. These results show that opioids modify endogenous opioid systems in the central nervous system and provide further support for the hypothesis. Such changes may contribute to the mechanisms of opiate dependence and abstinence.