【作者】 薛晓斌；

【导师】 缪竞诚；

【作者基本信息】 苏州大学 ， 免疫学， 2011， 硕士

【摘要】 目的:本研究采用临床病例-对照及病例自身对照研究,探讨非经典抗精神病药利培酮和齐拉西酮对精神分裂症患者血糖、胰岛素、瘦素、血脂及血浆细胞因子水平的影响,并对此进行比较分析。方法:患者组50例,其中利培酮组和齐拉西酮组各25例,对照组50例。所有入组者于入组次日及治疗8周后晨6时抽取空腹静脉血,以自动化分析仪器测定空腹血糖(FBG)及血脂各指标;采用电化学发光分析仪测定胰岛素各指标;采用酶联免疫吸附法(ELISA)测定细胞因子水平。所有入组的研究对象及患者的监护人均对本研究知情同意。用SPSS11.0软件包进行分析处理,实验数据用均数±标准差(X±S)做统计描述,治疗前后组内比较采用配对t-检验,组间比较采用独立样本t-检验。P<0.05为差异有显著性。结果:(1)治疗前利培酮组和齐拉西酮组两组间血糖、胰岛素、瘦素和血脂水平比较无显著性差异(P>0.05)。(2)精神分裂症患者经利培酮治疗8周后,FBG水平升高,FINS水平及IRI升高,ISI降低,各指标与治疗前比较均有显著差异(P<0.01);经齐拉西酮治疗8周后,FBG水平与治疗前比较无显著性差异(P>0.05),而Fins水平及IRI升高,ISI降低,与治疗前比较有显著性差异(P<0.01)。(3)精神分裂症患者经利培酮治疗8周后,TC、TG、LDL-C、Lep水平均有升高,与治疗前比较有显著差异(P<0.01),而HDL-C水平无显著性差异(P>0.05);经齐拉西酮治疗8周后,TG、LDL-C、Lep水平均明显升高,与治疗前比较有显著性差异(P<0.01),TC、HDL-C水平与治疗前比较无显著性差异(P>0.05)。(4)利培酮和齐拉西酮组治疗前后IL-2、IL-6和TNF-a均高于对照组,两组间比较均有显著性差异(P<0.01);治疗8周后,IL-2、IL-6、IL-12及TNF-a水平均有降低,与治疗前比较有显著差异(P<0.01)。结论:(1)抗精神病药物能够不同程度的影响机体的糖脂代谢及部分激素水平的含量,增加了心脑血管疾病、高血压、糖尿病等的发病风险,产生的可能机制有待于进一步的研究证实。(2)精神分裂症存在细胞因子介导的免疫功能障碍,表现为血浆细胞各因子含量升高,提示细胞因子水平升高可能与精神分裂症的发病过程有关。(3)抗精神病药物利培酮和齐拉西酮均对细胞因子具有调节作用,可能通过抑制细胞因子的有关机制产生免疫抑制作用,表现为抗精神病药物治疗后,各细胞因子水平明显下降。提示这可能是该药物的药理作用机制之一。(4)精神分裂症在缓解期仍存在着免疫功能障碍,表现为随着精神症状的缓解,细胞因子水平虽有明显改善,但仍未恢复到正常水平。提示该免疫功能在疾病的缓解期可能反映了精神分裂症有遗传性背景。更多还原

【Abstract】 Objective: The purpose of this study was to investigate glucose, serum lipid, insulin, leptin and plasma cytokines levels in schizophrenia patients, and further to understand the influence of antipsychotic on glucose, serum lipid, insulin, leptin and plasma cytokines.Methods: The case-control and self-control study were used. The study recruited 50 schizophrenia patients and 50 healthy controls matched by age, educational level and sex. All those patients take fasting blood sample at 6 o’clock in the morning before and after 8 weeks’treatment, and the controls take fasting blood sample at 6 o’clock in the morning. Fasting blood glucose and blood lipid levels were measured with Automated analyzer, and fasting insulin levels were measured with electrochemilumine scence analyzer, and plasma cytokines levels were measured with enzyme linked immunosorbent assay (ELISA). All experimental data were analyzed with SPSS14.0 statistical software, and were expressed as means and standard deviations ( x±SD). All data were analyzed with independence sample t-test and matched-pairs t-test. All p values were two-tailed, and P<0.05 for the difference was significant.Results: (1) There were no significant differences between risperidone groups and ziprasidone groups on the levels of blood glucose, insulin, leptin and blood lipids before treatment (P> 0.05). (2) After using risperidone, The FBG levels, Fins levels and IRI increased and ISI decreased significantly, there were significant differences (P <0.01). After using ziprasidone, the Fins level and IRI increased, and ISI decreased significantly (P <0.01), while the FBG levels were no significant changes (P>0.05). (3) After using risperidone, TC, TG, LDL-C and Lep levels increased significantly (P <0.01), while HDL-C levels were no significant differences (P> 0.05). After using ziprasidone, TG, LDL-C and Lep levels were significantly increased (P <0.01), and TC and HDL-C levels had no significant differences (P>0.05). (4) IL-2, IL-6 and TNF-a levels before and after risperidone and ziprasidone’s treatment were all higher than the control groups, there were significant differences (P <0.01). After using risperidone and ziprasidone, IL-2, IL-6 and TNF-a levels decreased significantly (P <0.01).Conclusion: (1) Antipsychotic drugs affected the glucose, lipid and some hormone levels, which could increase the risk of cardiovascular diseases, hypertension and diabetes. The possible mechanisms need to be confirmed by further studies. (2) Schizophrenia patients had cytokine-mediated immune dysfunction. It showed that the change of plasma cytokines levels maybe related to the pathogenesis of schizophrenia. (3) Risperidone and ziprasidone could regulate the plasma cytokines levels, and educed immunosuppression function, which might be one of the mechanisms of the pharmacological effects. (4) Schizophrenia patients still had immune function dysfunction in remission, which suggested that the dysfunction may be a genetic trait of schizophrenia.更多还原