【摘要】 背景:白细胞介素6是机体在免疫活动过程中产生的一种细胞因子。首发女性精神分裂症患者在服用氯氮平治疗后血清中白细胞介素6的变化是否为药物直接作用的结果及其是否与精神病症状的变化直接相关等问题尚需探讨。目的:观察女性首发精神分裂症患者血清白细胞介素6水平变化及其与氯氮平用量和症状改善的关系。设计:非随机同期病例-对照观察。单位:新乡医学院第二附属医院精神科。对象:于2005-05/12选取河南省精神病医院收治的精神分裂症女性患者20例为精神分裂症组。均符合中国精神障碍分类与诊断标准第3版精神分裂症的诊断标准;阳性症状与阴性症状量表评分>60分;未经治疗或门诊治疗至少2周未用药。排除有躯体疾病、内分泌及免疫系统疾病、营养不良及其他精神疾患,有过敏及激素治疗史,接受过免疫制剂治疗,近期内进行预防接种,怀孕或哺乳期妇女。对照组:同期选取年龄、性别与精神分裂症组差异无显著性意义的健康女性志愿者20例,排除标准同精神分裂症组。入组时均经受试者或监护人知情同意。方法:精神分裂症组患者均单一使用氯氮平,以25～50mg/d开始逐渐加量,3周内加到最大剂量,以最大疗效和最小副作用为用药原则。①采用酶联免疫吸附法测定精神分裂症组患者治疗前及治疗后第1,2,4周血清白细胞介素6水平。②采用高效液相色谱法测定氯氮平含量,以对照组受试者血清白细胞介素6水平作对照。③精神症状变化与白细胞介素6变化的相关分析:将患者治疗前、治疗后1,2,4周血清白细胞介素6水平分别与对应时段的阳性症状与阴性症状量表阳性症状分、阴性症状分、一般病理分、总分进行相关分析。主要观察指标:①氯氮平治疗前及治疗后各时间点患者血清白细胞介素6水平。②血清白细胞介素6水平与氯氮平含量的相关分析。③精神症状变化和血清白细胞介素6水平变化的相关分析。结果:①氯氮平治疗前及治疗后各时间点患者血清白细胞介素6水平:精神分裂症组患者治疗前血清白细胞介素6水平显著高于对照组[分别为(137.72±18.84),(65.05±20.95)ng/L,t=11.53,P<0.01],治疗后第1,2,4周均显著低于对照组[分别为(28.11±5.42),(8.48±1.14),(13.90±2.55),(65.05±20.95)ng/L,t=7.63,12.01,10.84,P<0.01]。②血清白细胞介素6水平与氯氮平含量的相关分析:治疗后第1,2,4周血清白细胞介素6水平与氯氮平含量均无显著相关性(r=-0.15,0.12,-0.29,P>0.05)。③精神症状变化和血清白细胞介素6水平变化的关系:精神分裂症组患者治疗前白细胞介素6水平与阳性症状分呈显著正相关(r=0.386,P<0.01),治疗后1,2,4周血清白细胞介素6水平与阳性症状与阴性症状量表总分及各因子分相关分析结果显示无显著相关性(r=0.136～0.237,P>0.05)。结论:女性首发精神分裂症患者血清白细胞介素6水平高于健康女性,氯氮平治疗可降低患者血清白细胞介素6水平,精神分裂症状改善与白细胞介素6变化无显著相关性。更多还原

【Abstract】 BACKGROUND: Interleukin-6 (IL-6) is a cytokine produced in the process of organic immune activities. The problems still need further exploration, including whether the changes of serum level of IL-6 after clozapine treatment ware induced directly by the drug, and whether IL-6 is directly correlated with the changes of the psychiatric symptoms in female patients with first-episode schizophrenia. OBJECTIVE: To explore the changes of the serum level of IL-6 and its relation with the dose of clozapine and the amelioration of the symptoms in female patients with first-episode schizophrenia. DESIGN: A non-randomized case-control observation synchronically. SETTING: Department of Psychiatry, Second Affiliated Hospital of Xinxiang Medical College. PARTICIPANTS: Twenty female patients with first-episode schizophrenia (patient group) were selected from Henan Psychiatric Hospital. They all met the diagnostic standards of schizophrenia in the 3rd edition of Chinese Classification and diagnostic criteria of Mental Disorders (CCMD-3), their score of positive and negative syndrome scale (PANSS) was above 60 points, and had not been treated or at least not taking medicine for 2 weeks during clinical treatment. Patients with physical disease, endocrine and immune system diseases, malnutrition and other mental problems, those with the history of being allergic and hormone treatment, those receiving immune pharmaceutical treatment, and recently having been vaccinated preventively, and the pregnant and breast-feeding women were excluded. Twenty healthy female volunteers, who had no significnat difference in age and gender from the subjects in the patient group, were taken as the control group, and the exclusive standards were the same as those in the patient group. All the subjects were enrolled with the approval of themselves and their guardians. METHODS: All the patients were adminsitrated with clozapine only, with the dose being added by 25-50 mg per day, and the maximal dose was reached within 3 weeks. The principle for the administration was the maximal effectiveness and the minimal side effect. ① Serum level of IL-6 in the patient group was detected using enzyme-linked immunoabsorbent assay (ELISA) before treatment and at 1, 2 and 4 weeks after treatment respectively. ② High performance liquid chromatography (HPLC) was used to determine the content of clozapine, and the levels of IL-6 in serum of the controls were taken as controls. ③ Correlations were analyzed in the patient group between the serum level of IL-6 before treatment and at 1, 2 and 4 weeks after treatment and the PANSS scores (scores of positive and negative symptoms, and general pathology, and the total score) at corresponding time points. MAIN OUTCOME MEASURES: ① Serum levels of IL-6 before treatment and at each time point after treatment; ② Correlation analysis between the serum levels of IL-6 and clozapine content; ③ Correlation analysis between changes of schizophrenic symptoms and serum levels of IL-6. RESULTS: ① Serum level of IL-6 before treatment in the patient group was significantly higher than that in the control group (137.72±18.84), (65.05±20.95) ng/L, t =11.53, P < 0.01, those in the patient group at 1, 2 and 4 weeks after treatment were significantly lower than that in the control group (28.11±5.42), (8.48±1.14), (13.90±2.55), (65.05±20.95) ng/L, t =7.63, 12.01, 10.84, P < 0.01. ② Correlation analysis between the serum levels of IL-6 and clozapine content: The results showed that the serum level of IL-6 had no significant correlation with the clozapine content at 1, 2 and 4 weeks after treatment (r =-0.15, 0.12, -0.29, P > 0.05). ③ Correlation analysis between IL-6 level and schizophrenic symptoms: In the patient group, there was significant positive correlation before treatment between the serum level of IL-6 and the score of positive symptoms (r =0.386, P < 0.01), and there was no significant correlation between the serum level of IL-6 and the total scores of PANSS and each factor scores at 1, 2 and 4 weeks after treatment (r =0.136-0.237, P > 0.05). CONCLUSION: The serum level of IL-6 in female patients with first-episode schizophrenia was higher than that in healthy females, and it could be decreased by clozapine, and the amelioration of the schizophrenic symptoms had no significant correlation with the changes of IL-6 levels.更多还原