目的:探讨吗啡与gp120致大鼠学习记忆障碍的作用与机制。方法:4~6周的SD大鼠,侧脑室注射吗啡与gp120 V3环,Morris水迷宫评价空间记忆能力。TUNEL染色观察大鼠海马组织的阳性凋亡细胞数。Western blot法检测p-ERK的表达情况。结果:与对照组相比,100μg/kg吗啡组、200μg/kg吗啡组以及gp120 V3环组均能使大鼠的逃避潜伏期延长(P〈0.05),目标象限停留时间以及穿越目标象限次数减少(P〈0.05),海马区阳性细胞数增多(P〈0.01),海马区p-ERK的表达增多(P〈0.01);200μg/kg吗啡+gp120 V3环组与200μg/kg吗啡组或gp120 V3环组相比,逃避潜伏期延长(P〈0.05),目标象限停留时间以及穿越目标象限次数减少(P〈0.05),海马区阳性细胞数增多(P〈0.01),海马区p-ERK的表达增多(P〈0.01)。结论:侧脑室注射gp120 V3环可致大鼠学习与记忆障碍,吗啡能增强其效应,机制可能与增强海马区p-ERK的表达有关。
AIM: To explore the role of morphine and gp120 V3 loop in learning and memory dysfunction in rats. METHODS: SD rats( 4 ~ 6 weeks old) were infused by the intracerebroventricular injection with gp120 V3 loop and morphine. The Morris water maze was used to evaluate spatial memory. The apoptotic cells in the hippocampal zone were observed by TUNEL staining. The protein level of p-ERK was determined by Western blot. RESULTS: Compared with control group,the rats exhibited a longer latency to escape the hidden platform,shorter retention and less frequency of crossing target quadrant in 100 μg / kg morphine group,200 μg / kg morphine group and gp120 V3 loop group. The TUNEL positive cells in the hippocampal zone of the rats in 100 μg / kg morphine group,200 μg / kg morphine group and gp120 V3 loop group were increased. The levels of p-ERK were also increased in 100 μg / kg morphine group,200 μg / kg morphine group and gp120V3 loop group as compared with the controls. The same results were observed in 200 μg / kg morphine +gp120 V3 loop group as compared with 200 μg / kg morphine group or gp120 V3 loop group. CONCLUSION: Intracerebroventricular injection of gp120 V3 loop induces learning and memory dysfunction in SD rats,and morphine enhances this effect. The mechanism may be related to the combined effect on the increase in p-ERK by gp120 V3 loop and morphine.