越鞠丸对皮质酮模型小鼠抑郁样行为和神经新生的影响

Effect of Yueju pill on depressive-like behavior and neurogenesis in corticosterone induced mice

目的探讨越鞠丸对慢性皮质酮诱导小鼠的抑郁样行为及神经新生的作用。方法 C57BL/6N小鼠进行皮质酮注射造模及给药,行为学检测模型及药效,免疫组化法比较小鼠海马DG区Ki67^+细胞数量,蛋白免疫印迹法检测PKA-ERK-CREB信号通路的表达变化。结果糖水偏好结果显示,皮质酮诱导小鼠糖水偏好程度明显下降,越鞠丸则能逆转这一表型;悬尾测试和陌生环境摄食测试的结果与糖水偏好结果相类似。免疫组化结果显示,皮质酮诱导小鼠海马DG区Ki67^+细胞数量明显减少,而越鞠丸能够增加阳性细胞数量。蛋白免疫印迹结果显示,皮质酮诱导小鼠海马中PKA、CREB、ERK的表达水平均明显下调,而越鞠丸则可以上调这些蛋白表达。结论在皮质酮诱导抑郁模型小鼠中,越鞠丸通过激活PKA-ERK-CREB信号通路,进而增强海马神经新生,从而起到抗抑郁的作用。

Aim To investigate the effects of Yueju pill on depressive-like behavior and neurogenesis in chronic corticosterone(CORT) induced mice. Methods Male C57BL/6N mice received chronic administration of CORT as well as Yueju pill. Behavioral tests were performed after the completion of treatment. The number of Ki67^+ cells in the hippocampal DG region of each group was counted by immunohistochemistry test.Meanwhile, the expression levels of PKA, ERK and CREB were detected by Western blot. Results The sucrose preference notably decreased( P <0.05) in CORT-induced mice in SPT, and it was raised obviously after Yueju treatment. The TST and NSF test displayed the similar results. The immunohistochemistry showed that the number of Ki67^+ cells in the hippocampus DG significantly decreased in CORT-induced mice, while the number of Yueju group apparently increased( P <0.05). Western blot showed that compared with control group, the protein expressions of PKA-ERK-CREB pathway were down-regulated in CORT-induced mice, which were up-regulated after Yueju treatment( P <0.05). Conclusions In CORT induced mice, Yueju pill can enhance the hippocampal neurogenesis by activating the PKA-ERK-CREB signaling pathway to display antidepressant-like effect.