急性吗啡耐受大鼠脑内孤啡肽含量和释放量变化的研究  

CHANGES OF THE CONTENT AND RELEASE OF OFQ IN BRAIN OF ACUTE MORPHINE TOLERANT RATS

作　　者：袁立[1,2] 田津斌 张肇康[1,2] 韩济生 

机构地区：[1]北京医科大学神经科学研究所 [2]美国凤凰制药有限公司

出　　处：《中国疼痛医学杂志》1999年第1期36-40,共5页Chinese Journal of Pain Medicine

基　　金：国家自然科学基金;国家攀登计划资助;美国NIDA基金

摘　　要：目的：应用放射免疫分析方法检测急性吗啡耐受过程中大鼠脑室灌流液、中脑导水管周围灰质（ＰＡＧ）及杏仁核中孤啡肽（ＯＦＱ）免疫活性（ｉｒ）的动态变化。结果：（１）每２小时皮下注射盐酸吗啡１次（７ｍｇ／ｋｇ），连续注射８次，造成急性吗啡耐受。此组大鼠脑室灌流液中ＯＦＱｉｒ较生理盐水对照组升高４０％，差异显著（Ｐ＜０．０５）。（２）皮下注射吗啡１、６、８次的大鼠ＰＡＧ中ＯＦＱｉｒ含量呈逐渐增长趋势，分别较生理盐水组升高９％（Ｐ＞０．０５）、３５％（Ｐ＜０．０５）和６０％（Ｐ＜０．０１）。（３）皮下注射１次吗啡的大鼠杏仁核中ＯＦＱｉｒ与生理盐水组相比，降低１１％，但无统计学意义；至第８次吗啡注射后较对照组升高４１％（Ｐ＜０．０５）。结论：多次注射吗啡能引起大鼠脑内ＯＦＱ含量和释放增多，结合以往关于ＯＦＱ在脑内对抗吗啡镇痛的事实表明内源性ＯＦＱ可能参与急性吗啡耐受的形成。Aim: To observe the changes of OFQ ir content in periaqueductal gray (PAG), amygdala and in cerebroventricular perfusate of acute morphine tolerant rats by radioimmunoassay (RIA). Results: (1) Acute morphine tolerance was produced in rats by 8 successive injections of morphine (7mgkg, s.c.) at intervals of 2 h. The content of OFQ ir in cerebroventricular perfusate in rats receiving 1 or 6 injections of morphine was found of no significant difference in comparison with normal saline (NS) control group, yet after 8 injections there was an increase of 40% ( P <0.05) compared with control group. (2) The content of OFQ ir in PAG of rats receiving 1, 6 or 8 injections of morphine showed an increase of 9% ( P >0.05), 35% ( P <0.05) and 60% ( P <0.01) respectively over NS control group. (3) The content of OFQ ir in amygdala of rats receiving 1 or 6 injections of morphine remained the same level as control group ( P <0.05), yet increased 41% ( P <0.05) after 8 injections. Conclusion: Considering the previous finding of the anti opioid effect of OFQ in the brain, the increased content and release of OFQ in rat brain may play important roles in the in vivo mechanism for the development of acute morphine tolerance.

关 键 词：孤啡肽 急性 吗啡 耐受性 中脑导水管 周围灰质 

分 类 号：R338.3[医药卫生—人体生理学]