双相障碍与脑源性神经营养因子外周血mRNA和蛋白表达相关性的研究

Brain-derived neurotrophic factor gene mRNA and protein expression in patients with bipolar disorder

目的探讨脑源性神经营养因子（BDNF）外周血mRNA表达和血清蛋白水平与双相障碍、双相躁狂和双相抑郁的关系。方法应用TaqMan探针及荧光实时定量逆转录一聚合酶链反应方法，检测并比较双相障碍组（61例）、双相躁狂组（29例）、双相抑郁组（32例）和对照组（61名）外周血白细胞BDNF基因的mRNA表达水平的差异；采用酶联免疫吸附方法测定血清BDNF浓度；应用17项汉密尔顿抑郁量表（HAMD17）和Young氏躁狂量表（YMRS）评定患者抑郁症状严重程度和躁狂症状的严重程度，采用Pearson相关分析分析BDNF基因mRNA表达水平和血清蛋白浓度与HAMD17和YMRS评分的关系。结果（1）双相障碍组BDNF基因mRNA相对表达水平（0．0077±0．0019）较对照组（0．0096±0．0028）下降（t=-3．74，P〈0．01）；双相躁狂组（0．0081±0．0023）、双相抑郁组（0．0073±0．0024）与对照组3组问BDNF基因mRNA相对表达水平的差异有统计学意义（F=7．55，P〈0．01），且双相躁狂组和双相抑郁组均低于对照组（P〈0．05或P〈0．01）。（2）双相障碍组BDNF血清蛋白浓度低于对照组（t=-2．90，P〈0．01）；双相躁狂组、双相抑郁组与对照组3组问BDNF血清蛋白浓度的差异有统计学意义（F=4．21，P〈0．05）；双相躁狂组和双相抑郁组BDNF血清蛋白浓度均低于对照组（P均〈0．05），但双相躁狂组与双相抑郁组比较差异无统计学意义（P〉0．05）。（3）双相躁狂组BDNF基因mRNA表达水平及血清蛋白浓度与YMRS评分未见相关（P〉0．05），双相抑郁组BDNF基因mRNA表达水平及血清蛋白浓度与HAMD17评分未见相关（P〉0．05）。结论双相障碍与BDNF水平下调可能相关，这种下降贯穿于躁狂相和抑郁相，而且BDNF的变化不会因双相障碍患者极性的变化而处于两极状态。

Objective To explore the association of peripheral brain-derived neurotrophic factor （BDNF） gene expression and serum protein levels with bipolar disorder （BPD）. Methods The real-time quantitative reverse transcriptase polymerase chain reaction （ RT-qPCR ） with TaqMan MGB was used to analyze the BDNF gene mRNA expression in peripheral lenkocytes of 61 patients with BPD[ 32 cases with bipolar mania（ BM）, 29 with bipolar depression（BD） ] and 61 healthy controls. The serum BDNF level was measured with enzyme-linked immunosorbent assay （ELISA） method. The symptoms of the patients were assessed with the Hamilton Depression Rating Scale-17 （HAMD17） and Young Mania Rating Scale （YMRS）. Results （1） The BDNF gene mRNA expression level in BPD group （0. 0077 ± 0. 0019 ） was significantly lower than that in control group （0. 0096 ± 0. 0028 ） （ t = - 3.74, P 〈 0. 01 ）. There was significant difference among three groups on BDNF expression （ BM： 0. 0081 ± 0. 0023, BD： 0. 0073 ±0. 0024; F = 7.55, P 〈 0. 01 ）. Furthermore, BDNF gene mRNA decreased both in BM and BD group compared with that in controls （ P 〈 0. 05, P 〈 0. 01, respectively ）. However, no difference was found between BM and BD groups （P 〉0.05）. （2） BDNF serum levels in BPD group （2. 80 ±0. 19） was lower than that in control group （2. 99 ± 0. 49） （ t = - 2. 90, P 〈 0. 01 ）. There was significant difference among three groups on BDNF expression （BM：2.81 ±0.17, BD：2.79 ±0,21; F = 4,21, P 〈0,05）. Furthermore, BDNF serum levels decreased in both BM and BB compared with those in controls （ all P 〈 0. 05, respectively）. However no difference was found between BM and BD （P 〉 0. 05 ）. （3） Neither the expression levels nor serum levels of BDNF in BM were correlated with YMRS （ P 〉 0.05 ） , and the same result was found in BD group （ P 〉 0. 05 ）. Conclusions The findings suggest that the decreased BDNF levels may be involved in the pathophysiology of BPD, while BDNF levels might not have polarized changes in different status of episodes.