吗啡依赖及戒断大鼠糖皮质激素及其受体mRNA表达水平的改变

目的:研究慢性吗啡处理和吗啡戒断对大鼠血清中ACTH及其受体mRNA表达水平的影响。方法:利用放射免疫法测定吗啡依赖及戒断大鼠血清中ACTH及皮质醇的浓度;利用核酸分子杂交技术研究下丘脑糖皮质激素受体(GR)基因表达的改变情况。结果:(1)吗啡依赖组大鼠血清中ACTH及皮质醇的浓度明显低于对照组;戒断d1大鼠血清ACTH浓度仍明显低于对照组(P<0.01),但血清皮质醇的浓度则明显高于对照组(P<0.01);戒断d7大鼠血清ACTH浓度与对照组比较,无显著性差异(P>0.05),而血清皮质醇的浓度仍略高于对照组(P<0.05);(2)吗啡依赖组大鼠下丘脑GR基因表达水平下降(P<0.05),戒断组大鼠GR的基因表达均高于对照组,但无显著性差异(P>0.05)。结论:吗啡类物质的长期使用可以对下丘脑-垂体-肾上腺轴的激素分泌功能及GR的基因表达产生明显的抑制作用。

THE CHANGES OF GLUCOCORTICOIDS AND mRNA IN RATS OF MORPHINE DEPENDENCE AND WITHDRAWAL

Objective: To study the changes of glucocorticiods and mRNA in the rats of morpinne dependence and withdrawal. Methods: ACTH and cortisol concentration of morpinne dependent and withdrawn rats were determined by radioimmunoassay. The hypothalamus GR gene expression was investigated by dot and northern blot hybridization. Results: Compared with control group, the ACTH and cortisol levels in morpinne dependent rats reduced apparently (P < 0.01). On the first day of withdrawal , the ACTH level was still lower than that of the control( P < 0.01), winle cortisol level increased acutely( P < 0.01). On the seventh day of withdrawal, the ACTH level increased to the normal, winle cortisol level was still ingher than that of the control(P < 0.05). GR gene expression decreased in morpinne dependent group(P < 0.05) ,but increased in morpinne withdrawn group. Conclusion : Long - term opiates administration can ininbit the function of HPA axis and its mRNA.