糖原合成酶激酶3β对小补心汤总黄酮治疗皮质酮诱导抑郁模型小鼠影响的研究

Effect of glycogen synthase kinase 3β on treatment of corticosterone-induced depression in mice treated with Xiaobuxintang-2

目的:小补心汤总黄酮具有抗抑郁的作用,然而其潜在的机制尚不清楚。本研究利用皮质酮诱导的小鼠抑郁模型,研究小补心汤总黄酮的抗抑郁作用及其潜在机制。方法:通过皮质酮诱导小鼠抑郁模型,小鼠分为5组(Ⅰ)对照组;(Ⅱ)皮质酮(CORT)组;(Ⅲ)皮质酮+小补心汤总黄酮(CORT+XBXT-2)组;(Ⅳ)皮质酮+小补心汤总黄酮+慢病毒空载(CORT+XBXT-2+空载)组;(Ⅴ)皮质酮+小补心汤总黄酮+慢病毒GSK3β过表达(CORT+XBXT-2+GSK3β)组。通过免疫印记检测海马中GSK3β表达水平,通过强迫游泳试验和悬尾试验评估小鼠的抑郁状态。结果:定位注射GSK3β慢病毒后诱导小鼠海马部位特异性高表达GSK3β,其mRNA和蛋白水平均明显提高。与对照组相比,皮质酮注射诱导抑郁模型的小鼠(CORT组)的不动时间显著增加,而小补心汤总黄酮可以有效降低小鼠的不动时间。过表达GFP空载慢病毒不影响小鼠的行为,而过表达GSK3β显著增加小鼠在强迫游泳试验和悬尾试验中的不动时间。结论:在小鼠海马部位特异性高表达GSK3β可以抑制小补心汤总黄酮对皮质酮诱导的抑郁小鼠的治疗作用。

Objective: Xiaobuxintang-2(XBXT-2)has antidepressant effects,but the underlying mechanism is still unclear.In this study,we used the corticosterone-induced depression mouse model to study the antidepressant effect of XBXT-2and its underlying mechanisms.Methods: A mouse model of depression was induced by corticosterone.The mice were divided into 5 groups(a)control group,(b)corticosterone group(CORT),(c)corticosterone+XBXT-2(CORT+XBXT-2)group,(d)corticosterone+XBXT-2+lentiviral empty group(CORT+XBXT-2+no-load),(e)corticosterone+XBXT-2+lentivirus GSK3βoverexpression group(CORT+XBXT-2+GSK3β).The expression level of GSK3βin the hippocampus was detected by immunoblotting,and the depression status of the mice was evaluated by forced swimming test and tail suspension test.Results: The GSK3βlentivirus induced the high expression of GSK3βin the hippocampus of mice,and the mRNA and protein levels were significantly increased compared with the control group.The immobility time significantly increased in corticosterone injection-induced depression model mice(CORT group),and XBXT-2 can effectively reduce the immobility time of depression model mice.Overexpression of GFP empty lentivirus did not affect mouse behavior,whereas overexpression of GSK3βsignificantly increased immobility time in depression model mice according to forced swimming and tail suspension experiments.Conclusion: High expression of GSK3βin the hippocampus of mice can inhibit the therapeutic effect of XBXT-2 on the corticosterone-induced depression in mice.