白介素-1β基因多态性及核因子-κB对精神分裂症首次发病患者血清白介素-1β水平的影响  

Effects of interleukin-1β gene polymorphism and nuclear factor-κB activation on IL-1β levels in firstepisode schizophrenia

作　　者：宋学勤[1] 吕路线[2] 李文强[2] 仲昭夕[2] 李幼辉[1] 郝以辉[1] 赵靖平[3] 

机构地区：[1]郑州大学第一附属医院精神医学科,450052 [2]河南省精神病医院 [3]中南大学湘雅二医院精神卫生研究所

出　　处：《中华精神科杂志》2012年第1期10-15,共6页Chinese Journal of Psychiatry

基　　金：国家自然科学基金资助项目（30870892、30971058、81071090）;卫生部科研基金资助项目（200801009）;河南省基础与前沿研究项目（102300413208）

摘　　要：目的探讨精神分裂症患者白介素-10（IL-1β）基因多态性及核因子-κβ（NF—κβ）对IL-1β水平的影响。方法采用聚合酶链反应-限制性内切酶方法检测161例精神分裂症患者（患者组）和135名正常对照者（对照组）的IL-1β基因-511多态性位点和＋3953多态性位点的基因型及等位基因频率；采用酶联免疫吸附法检测IL-1β在患者组和对照组血清中的蛋白表达及外周血单个核细胞（PβMC）NF—κβ活性；采用逆转录-聚合酶链反应方法检测PβMC IL-1βmRNA表达水平。结果（1）IL-1β-511G／A位点的等位基因G与精神分裂症存在名义上的关联（P=0．038，多重检验P=0．240），但＋3953G／A多态性与精神分裂症无关联（P〉0．05）。（2）患者组血清IL-1β水平[（25．93±13．30）ng/L]、PBME中IL-1βmRNA（1．30±0．30）表达以及NF-κβ活性[（0．28±0．21）μg／L]均高于对照组[（14．19±7．86）ng／L、0．97±0．27、（0．20±0．17）μg/L；P均〈0．05]；携带IL-1β基因-511A／G和＋3953A／G位点基因型GA和AA的精神分裂症患者较GG携带者的IL-1β水平明显增高（P〈0．05）。结论精神分裂症患者外周血IL-1β水平的增高参与了疾病的病理生理过程，基因多态性和转录因子NF—κB均对细胞因子的分泌起了-定作用。Objective To explore the effects of interleukin-1β （IL-1β ） gene polymorphism and nuclear factor-κB on serum IL-1β level in schizophrenia. Methods Amplification of the target site in the IL- 1β gene -511 and ＋3953 were carried out by polymerase chain reaction （PCR） in 161 patients who met the CCMD-3 diagnostic criteria for schizophrenia and 135 healthy control subjects. The allelic and genotypic types were determined by restriction fragment length polymorphism. The serum IL-1β level and peripheral blood mononuclear cell （ PBMC ） NF-κB activation of 83 patients and 65 healthy control subjects were estimated using commercial enzyme-linked immunosorbent assay （ELISA） kits according to the manufacturer＇s instructions. Reverse transcription-polymerase chain reaction （RT-PCR） technique was applied to analyze PBMC mRNA expression of IL-1β. Results It showed a significant increase of the IL-1 [3 -511 allele G in schizophrenia patients as compared to healthy controls. While there were no relation between IL-1β ＋ 3953G/A and schizophrenia. Serum level （ 25.93± 13.30 ） ng,/L and PBMC mRNA expression（ 1.30 ±0. 30） of IL-1β and NF-κB activation（0. 28 ± 0. 21 ） Ixg/L in the schizophrenia group were significantly higher than those in the control subjects （ 14. 19± 7.86） ng/L, （0. 97 ± 0. 27 ）, （0. 20 ± 0. 17） pog/L respectively （P 〈0. 05）. Serum IL-1β levels in the subjects with AA and G/A genotypes were significantly higher than those of the subjects with GG genotype in the IL-1β gene -511 and ＋ 3953 target site. Conclusions The higher serum level of IL-1β in schizophrenia patients may be involved in the pathophysiology of schizophrenia. Gene polymorphism and nuclear factor-κB may be related to the secretion of cytokine.

关 键 词：精神分裂症 白细胞介素1Β 多态性 限制性片段长度 NF-κB 

分 类 号：R749.3[医药卫生—神经病学与精神病学]