氯胺酮与乙醇对小鼠海马PKA-CREB信号通路的影响

Effects of ketamine on ethanol-induced learning and memory impairment in mice

目的:研究氯胺酮与乙醇对小鼠海马PKA-CREB信号通路的影响,探讨氯胺酮与乙醇致学习记忆障碍的分子学机制。方法:40只ICR小鼠随机分为4组:对照组、氯胺酮组、乙醇组、氯胺酮乙醇合用组,每组10只。氯胺酮和乙醇分别采取腹腔注射和灌胃的给药方式,1次/d,连续14 d。通过RT-PCR检测海马中c-AMP反应单元结合蛋白(c-AMP response element binding protein,CREB)、蛋白激酶A(protein kinase A,PKA)及腺苷酸环化酶(adenylate cyclase,AC)mRNA的表达;Western Blot检测pCREB/CREB的蛋白表达。结果:RT-PCR检测结果 :氯胺酮乙醇合用组可显著降低海马区CREB、PKA及AC mRNA的表达(P<0.05),Western Blot检测显示pCREB/CREB的蛋白表达显著降低(P<0.05)。结论:氯胺酮与乙醇可协同抑制小鼠的学习记忆行为,其机制可能与大脑海马区CREB信号通路相关。

Objective： To study the effects of ketamine and ethanol on PKA-CREB pathway of hippocampus-dependent learning and memory in mice and its possible mechanism.Methods： A total of 40 male mice were divided into 4 groups： a normal control group,a ketamine group,an ethanol group and an ethanol plus ketamine group.Ketamine and ethanol were respectively taken by intraperitoneal injection and oral administration,once per day,for 14 d.The expressions of CREB,PKA and AC gene in hippocampus were detected by RT-PCR.The expressions of pCREB/CREB were detected by Western Blot.Results： After the combined treatment with ketamin and ethanol,CREB,PKA and AC mRNA were down regulated by RT-PCR（P〈0.05）,and pCREB/CREB were down regulated by Western Blot（P〈0.05）.Conclusion： The data indicate that combination of ketamine and ethanol is synergic in the inhibition of learning and memory in mice,its mechanism may be related to the CREB signal transduction pathway.