小檗碱合并利培酮对精神分裂症患者血清BDNF、CRP及认知功能影响研究

发布时间：2018-09-06 06:29

【摘要】：目的:精神分裂症是一种病因及发病机制未明的慢性重型精神疾病,除神经递质假说外,还可能与神经营养及神经损伤有关,炎性反应也可能在精神类疾病发展中起重要作用,尤其与精神分裂症的发生存在显著的相关性。精神分裂症进展过程中常常伴随着认知功能受损,严重影响精神分裂症患者的预后,成为公认的重大公共卫生难题。研究表明,小檗碱具有拮抗氧化应激,抑制炎症反应的作用。动物实验表明,它还具有保护神经细胞,改善学习记忆功能等作用。然而这一作用仅限于动物研究水平,临床研究未见报道。本课题探讨小檗碱对精神分裂症患者血清BDNF、CRP水平及认知功能的影响及其可能作用机制,为进一步探讨精神分裂症的发病机理,寻找新的治疗方法提供线索。方法:本研究采用随机双盲、安慰剂对照的研究方法,根据DSM-V关于精神分裂症的诊断标准选取精神分裂症住院患者64名,所有入组的受试者均使用利培酮单药治疗。随机将患者分为研究组与对照组,两组性别、年龄均相匹配,且维持入组时利培酮治疗剂量。研究组用药为利培酮合并小檗碱(300 mg TID)治疗,对照组用药为利培酮合并小檗碱安慰剂治疗,治疗周期为12周。受试者在第0周入组时进行基线测验,测量基线血清BDNF及CRP水平,进行认知功能测评,包括连线测验(TMTA)、符号编码测验(SC)、流畅性、迷宫测验、情绪智商测验、PSP量表评分。在研究的第12周末,重复上述测定内容,比较治疗前后上述指标的差异水平,评估小檗碱对精神分裂症患者血清BDNF、CRP水平及认知功能的影响。数据结果分析采用SPSS17.0统计软件包进行,P值小于0.05为差异具有显著性。结果:1、与基线相比,研究组血清BDNF水平在第12周末的差异具有统计学意义(P0.01);治疗后组间比较,研究组和对照组BDNF水平的差异均具有统计学意义(P0.05)。2、与基线相比,研究组CRP水平在第12周末的差异具有统计学意义(P0.01);治疗后组间比较,研究组和对照组CRP水平的差异均具有统计学意义(P0.05)。3、治疗12周末与基线相比,研究组在处理速度维度各项目、迷宫测验、情绪智商测验均有显著改善(P0.01);治疗后组间比较,研究组和对照组处理速度维度各项目粗分、情绪智商测验差异均具有统计学意义(P0.05)。4、治疗12周末与基线相比,研究组社会中有益的活动、个人关系和社会关系、自我照料、扰乱及攻击行为、PSP总分的差异具有统计学意义(P0.05);治疗后组间比较,研究组和对照组社会中有益的活动评分具有显著差异(P0.05)。结论:1、小檗碱可升高利培酮单药治疗的精神分裂症患者血清BDNF水平,具有神经保护作用。2、小檗碱可降低利培酮单药治疗的精神分裂症患者CRP水平,抑制炎症反应。3、小檗碱可显著改善利培酮治疗精神分裂症患者认知功能,对信息处理速度、社会认知、工作学习能力有改善作用,而对患者的执行功能并无改善作用。
[Abstract]:Objective: schizophrenia is a chronic severe mental disease with unknown etiology and pathogenesis. In addition to the neurotransmitter hypothesis, it may also be related to neurotrophic and nerve injury. Inflammatory reaction may also play an important role in the development of mental diseases. In particular, there is a significant correlation with the occurrence of schizophrenia. Cognitive impairment is often associated with the progression of schizophrenia, which seriously affects the prognosis of patients with schizophrenia and has become a recognized major public health problem. The results showed that berberine could antagonize oxidative stress and inhibit inflammatory reaction. Animal experiments show that it can also protect nerve cells and improve learning and memory function. However, this effect is limited to animal research level, clinical studies have not been reported. The purpose of this study was to investigate the effect of berberine on serum BDNF,CRP level and cognitive function and its possible mechanism in schizophrenic patients, and to provide clues for further exploring the pathogenesis of schizophrenia and finding new treatment methods. Methods: a randomized, double-blind, placebo-controlled study was conducted to select 64 schizophrenic inpatients according to DSM-V 's criteria for schizophrenia. All subjects were treated with risperidone alone. The patients were randomly divided into study group and control group. The study group was treated with risperidone combined with berberine (300 mg TID), the control group was treated with risperidone and berberine placebo for 12 weeks. At week 0, baseline test was performed, baseline serum BDNF and CRP levels were measured, and cognitive function was evaluated, including (SC), fluency, maze test and emotional intelligence quotient test (EIQ). At the end of the 12th week of the study, the above measurement was repeated to compare the difference of the above indexes before and after treatment, and to evaluate the effect of berberine on serum BDNF,CRP level and cognitive function in schizophrenic patients. Data analysis using SPSS17.0 statistical software package for P < 0. 05 had significant difference. Results compared with the baseline, the serum BDNF level of the study group was significantly different from that of the baseline (P0.01), and the difference between the study group and the control group was statistically significant after treatment (P0.05) .2Compared with the baseline. The difference of CRP level in the study group at the 12th weekend was statistically significant (P0.01); after treatment, the difference of CRP level between the study group and the control group was statistically significant (P0.05) .3.Compared with the baseline at the end of the 12th week, the study group was in each item of processing speed dimension. Labyrinth test and emotional IQ test were significantly improved (P0.01). After treatment, there were significant differences between the study group and the control group in the processing speed dimension of each item coarse score, emotional IQ test difference was statistically significant (P0.05) .4, 12 weeks after treatment compared with the baseline, There were statistically significant differences in the total scores of beneficial activities, personal relationships and social relations, self-care, disturbance and aggression in the study group (P0.05). There was significant difference in the score of beneficial activities between the study group and the control group (P0.05). Conclusion berberine can increase the level of serum BDNF in schizophrenic patients treated with risperidone, and has neuroprotective effect. Berberine can decrease the level of CRP in patients with schizophrenia treated with risperidone alone. Inhibition of inflammatory response. 3. Berberine can significantly improve the cognitive function of patients with schizophrenia treated with risperidone. It can improve the speed of information processing, social cognition and working and learning ability, but has no effect on the executive function of the patients.
【学位授予单位】：天津医科大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R749.3

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