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目的:研究磷脂酰肌醇3激酶(phosphatidylinositol 3 kinase，PI3K)抑制剂LY294002对AKT/GSK3β/CRMP2信号通路的影响，及通路改变对大鼠抑郁样行为及微管蛋白的影响。方法:16只成年雄性SD大鼠采用盲法随机分为LY294002组及溶剂DMSO组，每组8只。麻醉后进行海马CA1区脑立体置管，置管1周后给予LY294002或DMSO脑立体注射，并进行抑郁样行为检测。采用RT-qPCR技术检测海马AKT、GSK3β、CRMP2、tubulin的mRNA表达水平，采用Western blot检测海马AKT、p-AKT、GSK3β、p-GSK3β、CRMP2、p-CRMP2以及微管动态性相关蛋白Acet-tubulin、Tyr-tubulin表达水平。比较两组大鼠抑郁样行为表现及分子表达差异。结果:旷场实验显示，LY294002组大鼠的中心移动距离较DMSO组显著下降[(3.64±2.17)cm；(31.51±12.68)cm；n t＝2.69，n P＝0.03]；LY294002组中心区持续时间较DMSO组亦显著下降[(0.73±0.46)s；(4.85±2.10)s；n t＝2.33，n P＝0.04]。强迫游泳测试结果显示LY294002组大鼠的不动时间有升高的趋势，但差异无统计学意义。糖水偏好实验显示两组大鼠糖水消耗量差异无统计学意义(n P>0.05)。RT-qPCR结果显示，LY294002组大鼠海马组织CRMP2 mRNA表达水平显著下降(n P<0.05)。Western blot结果显示，与DSMO组比较，LY294002组大鼠海马组织p-AKT及p-GSK3β表达水平下降(n P<0.05)；CRMP2表达水平降低，p-CRMP2表达水平显著升高，同时，Tyr-tubulin表达水平下降，Acet-tubulin表达水平显著升高，两组均差异有统计学意义(均n P0.05). The RT-qPCR results showed that the expression level of CRMP2 mRNA in the LY294002 group decreased significantly (n P<0.05). Western blot results showed that compared with solvent DMSO group, the expression levels of p-AKT and p-GSK3β in the LY294002 group decreased (n P<0.05), the expression level of CRMP2 was decreased and the expression level of p-CRMP2 was significantly increased. At the same time, the expression level of Tyr-tubulin decreased, while Acet-tubulin level increased significantly, and the differences were statistically significant (n P<0.05).n Conclusion:LY294002 affects AKT/GSK3β/CRMP2 signaling pathway, induces impairment of microtubular dynamic, and results in depression-like behavior in rats.