吗啡依赖大鼠脑组织细胞色素P450侧链裂解酶表达水平的变化

目的 评价吗啡依赖大鼠脑组织细胞色素P450侧链裂解酶(P450scc)表达水平的变化.方法 雄性SD大鼠24只,月龄4～8月,体重180～200 g,随机分为3组(n=8):生理盐水对照组(NS组)、吗啡依赖组(MD组)和吗啡戒断组(MW组).MD组和MW组采用剂量递增法腹腔注射吗啡制备大鼠吗啡依赖模型,连续注射7 d,2次/d,剂量分别为5、10、15、20、30、40、50 mg/kg,NS组腹腔注射等容量生理盐水.NS组和MD组于末次给药1 h后断头处死大鼠,MW组于末次给药1 h时注射纳洛酮2 mg/kg,30 min后断头处死取脑,采用Western blot法检测大鼠额叶皮质、海马、纹状体、丘脑P450scc的表达水平.结果 P450scc在额叶皮质、海马、纹状体、丘脑均有表达;与NS组比较,MD组和MW组额叶皮质、纹状体和海马的P450scc表达水平降低(P<0.05).结论 脑组织P450scc表达下调可能与大鼠吗啡依赖的形成有关,而与吗啡戒断无关.

Changes in expression of cytochrome cholesterol side chain cleavage enzyme in the brain of morphine-dependent rats

Objective To evaluate the changes in the expression of cytochrome cholesterol side chain cleavage enzyme (P450scc) in the brain of morphine-dependent rats. Methods Twenty-four male SD rats aged 4-8 months weighing 180-200 g were randomly divided into 3 groups (n = 8 each): group Ⅰ normal saline (group NS), group Ⅱ morphine dependence (group MD) and group Ⅲ morphine withdrawal (group MW). In group MD and MW, the rats were given intraperitoneally increasing doses of morphine starting from 5 mg/kg to 10, 15, 20, 30, 40 and 50 mg/kg twice a day for 7 days. In group NS, the rats were given equal volume of normal saline instead of morphine. The rats were decapitated 1 h after last injection in group NS and MD. In group MW, naloxone 2 mg/kg was given 1 h after last injection, and then the animals were decapitated 30 min after withdrawal symptoms were observed. The brains were immediately removed and the frontal cortex, hippocampus, striatum and thalamus were separated. The expression of P450see was determined by Western blot. Results The expression of P450scc in the frontal cortex, hippocampus and striatum was significantly decreased in group MD and MW compared with group NS (P<0.05). Conclusion The down-regulation of P450scc expression might be involved in the development of morphine dependence, but it is not involved in the morphine withdrawal.