外源性硫化氢对吗啡成瘾大鼠海马区cAMP信号通路和学习记忆能力的影响（英文）

Effects of exogenous hydrogen sulfide on morphine dependent rats' learning and memory capacity and the cAMP signaling pathway in hippocampus

目的证实硫化氢能否调节吗啡成瘾大鼠海马区内腺苷酸环化酶通路,改善吗啡成瘾所导致的学习记忆相关的神经行为学影响。方法本实验中,应用Morris水迷宫来评估吗啡成瘾大鼠的学习记忆能力,酶联免疫试剂盒检测海马组织内腺苷酸环化酶、环磷酸腺苷及蛋白激酶A水平,免疫印迹法检测海马内磷酸化的环磷酸腺苷反应元件结合蛋白水平。结果 Morris水迷宫测试结果表明,外源性硫化氢能提高吗啡成瘾大鼠学习记忆能力。酶联免疫及免疫印迹检测结果表明,外源性硫化氢能够明显提高吗啡成瘾大鼠海马组织内腺苷酸环化酶、环磷酸腺苷、蛋白激酶A及磷酸化的环磷酸腺苷反应元件结合蛋白水平。此外,使用胱硫醚β合成酶抑制剂盐酸羥胺的吗啡成瘾大鼠海马组织内腺苷酸环化酶、环磷酸腺苷、蛋白激酶A及磷酸化的环磷酸腺苷反应原件结合蛋白水平与吗啡组大鼠无明显差异。结论外源性硫化氢提高吗啡成瘾大鼠海马组织内腺苷酸环化酶、环磷酸腺苷、蛋白激酶A及磷酸化的环磷酸腺苷反应元件结合蛋白水平,并改善吗啡成瘾大鼠学习记忆能力。

Objective To identify whether hydrogen sulfide（H2S） alleviates the morphine-induced neurobehavioral defects of learning and memory by inhibiting the AC/c AMP/PKA/CREB signaling pathway in hippocampus of morphine-dependent rats.Methods Morris water maze was used to evaluate learning and memory ability in morphine-dependent rats.The levels of AC,c AMP,PKA in hippocampus were detected by ELISA.The level of p-CREB protein in hippocampus was detected by western blot.Results Morris water maze test showed that exogenous H2 S improved the ability of learning and memory in morphine-dependent rats.ELISA and western blot revealed that exogenous H2 S significantly improved the levels of AC,PKA,c AMP and p-CREB.Moreover,after cystathionine-γ-lyase inhibitor hydroxylamine hydrochloride administration,the levels of AC,PKA,c AMP and p-CREB were also significantly suppressed in morphine-dependent rats.Conclusion We speculate that exogenous H2 S improves the learning and memory ability by up-regulating AC/c AMP/PKA/CREB signaling pathway in hippocampus of morphine-dependent rats.