摘要
目的:探讨碳酸锂联合奥氮平治疗对双相躁狂发作患者外周血单核细胞(PBMCs)糖原合成酶激酶3(GSK3)活性的影响。方法:21例双相I型躁狂发作患者给予碳酸锂合并奥氮平治疗8周,于治疗前、治疗4周和8周采集患者外周静脉血20ml,应用免疫印迹法检测PBMCs的GSK3α和GSK3β丝氨酸磷酸化水平以及总GSK3水平。同时采用杨氏躁狂量表(YMRS)、蒙哥马利抑郁量表(MADRS)以及临床疗效总评量表-病情严重程度(CGI-S)评定症状变化。结果:①治疗后YMRS、MADRS以及CGI-S评分较治疗前明显降低(P均<0.001);②治疗后PBMCs的pSer-GSK3α、pSer-GSK3β较治疗前升高,以pSer-GSK3β尤为明显,由治疗前的(53.44±17.57)%升高至治疗8周的(72.96±25.66)%。剔除躁狂发作次数≥3次者后比较,治疗8周pSer-GSK3β升高更为显著(P=0.022);③pSer9-GSK3β/to-tal-GSK3β比值与YMRS基线评分呈负相关(r=-0.-487,P=0.025)。结论:碳酸锂合并奥氮平治疗可以升高双相躁狂患者PBMCs的GSK3β磷酸化水平,降低GSK3活性。
Objective:To explore the impact of treatment of lithium and olanzapine on glycogen synthase kinase-3(GSK3) activity in the peripheral blood mononuclear cells(PBMCs) of patients with bipolar mania. Method:21 patients with bipolar I mania were enrolled and received treatment of lithium and olanzapine for eight weeks.20 ml of blood was collected from each patient by venipuncture at week 0,week 4 and week 8.The level of pSer21-GSK3α,pSer9-GSK3β,total GSK3α and GSK3β in PBMCs of patients were measured by western blot when blood samples of three visits were collected.Clinical symptoms were assessed with the Young mania rating scale(YMRS) ,the Montgomery-Asberg depression rating scale(MADRS) and the clinical global impression for bipolar disorder-severity(CGI-S) at the same time. Results:①The average scores of YMRS,MADRS,and CGI-S significantly reduced at week 8 compared with those at week 0(P0.001);②The level of pSer-GSK3α and pSer-GSK3β increased at week 8.The increase was especially apparent in pSer-GSK3β from(53.44±17.57) at week 0 to(72.96±25.66) at week 8;Excluding patients with manic episodes more than 3 times,there is a significant increase in pSer-GSK3β during the eight-week treatment(P=0.022);③There was a negative correlation between ratio of pSer-GSK3β to total-GSK3β and the average score of YMRS at week 0(r= -0.-487,P=0.025) . Conclusion:Lithium and olanzapine could increase the level of pSer-GSK3β in PBMCs of patients with bipolar mania and decrease GSK3 activity.
出处
《临床精神医学杂志》
2011年第6期415-419,共5页
Journal of Clinical Psychiatry