重性抑郁障碍外周血糖原合成酶激酶-3β差异表达研究

Differential expression of glycogen synthase kinase-3β in peripheral blood in major depressive disorder

目的初步探讨糖原合成酶激酶-3β(GSK-3β)在重性抑郁障碍(MDD)发生发展中的作用。方法通过免疫印迹法检测17例首发MDD患者治疗前后及17名健康对照组的外周血单核细胞GSK-3β、丝氨酸-9磷酸化GSK-3β(p-Ser9-GSK-3β)的蛋白水平及差异。结果 1患者组治疗前GSK-3β蛋白表达明显高于健康对照组(t=2.328,P<0.05);经氟西汀抗抑郁治疗后,GSK-3β与治疗前相比明显减少(t=-2.176,P<0.05);治疗后的GSK-3β和健康对照组差异无统计学意义(t=0.852,P>0.05)。2患者治疗前p-Ser9-GSK-3β的蛋白表达高于健康对照组(t=4.676,P<0.01);经氟西汀抗抑郁治疗后,p-Ser9-GSK-3β表达与治疗前相比增加(t=3.892,P<0.01);治疗后p-Ser9-GSK-3β和健康对照组相比差异有统计学意义(t=4.835,P<0.01)。结论 GSK-3β可能参与了MDD的发生及发展;氟西汀分散片可通过磷酸化GSK-3β使其失活,进而发挥抗抑郁作用。

Objective To investigate the role of the glycogen synthase kinase-3β（GSK-3β） in the occurrence and development of major depressive disorder（MDD）. Methods Western blotting was used to determine the protein levles of GSK-3β and Phospho-Ser9-GSK-3β（p-Ser9-GSK-3β） in the peripheral blood monouclear cells in 17 firstepisode MDD patients before and after treatment and the normal control group（n=17）, and the differences were compared. Results 1The GSK-3β protein expression in MDD patients was significantly higher than that in the normal controls（t=2.328, P〈0.05）. After antidepressant treatment with Fluoxetine, the expression level of GSK-3β was significantly decreased compared with that before the treatment（t=-2.176,P〈0.05）. There was no significant difference in the expression level of GSK-3β between the MDD patients after the treatment and the normal controls（t=0.852, P〈0.05）. 2The protein expression of p-Ser9-GSK-3β in the MDD patients before treatment was higher than that in the normal controls（t=4.676,P〈0.01）. After antidepressant treatment with Fluoxetine, the expression level of p-Ser9-GSK-3β was significantly decreased compared with that before the treatment（t=-3.892,P〈0.01）. There was significant difference in the expression level of GSK-3β between the MDD patients after the treatment and the normal controls（t=4.835, P〈0.01）. Conclusion GSK-3β may be involved in the occurrence and development of MDD. Fluoxetine dispersible tablets can inactivate w MDD by phosphorylated GSK-3β, and further play antidepressant effect.