神经精神狼疮患者认知功能及脑脊液生物标志物的相关研究

发布时间：2018-07-25 15:42

【摘要】：目的评估神经精神狼疮(NPSLE)患者认知功能情况及其脑脊液(CSF)中生物标志物的变化,研究患者认知功能障碍的模式。探索神经精神狼疮的有效的临床评估方法。方法通过词语学习量表(VLT)、词语流畅性测验、数字符号测验、复杂图形测验(CFT)、Stroop色词测验(CWT)、连线测验(TMT)、插孔试验等神经心理量表评估记忆、注意力、执行功能、视空间能力、运动及精神运动速度等认知领域并且通过蒙特利尔认知评估量表(MoCA)对所有受试者进行认知功能筛查；同时使用医院焦虑抑郁量表对患者进行情感异常方面的评估。收集和测定患者脑脊液中的白细胞介素6(IL-6)、白细胞介素8(IL-8)、干扰素伽马诱导蛋白10(IP-10)、单核细胞化学趋化蛋白1(MCP-1)、调解活化正常T细胞表达和分泌因子(RANTES)、巨噬细胞炎性蛋白3(MIP-3a)、基质金属蛋白酶9(MMP-9)、白细胞介素23(IL-23)的浓度。比较上述指标在NPSLE患者、无神经精神症状的系统性红斑狼疮患者及非自身免疫性疾病患者间的差异。结果NPSLE患者的认知功能在连线测验,复杂图形临摹,数字符号替换、Stroop色词测验和听觉词语学习测验中与对照组相比有显著性差异,提示在知领域均低于正常对照组,其中注意力、精神运动速度及词语记忆这几个认知领域与无神经精神症状的狼疮患者也有显著差异。并且NPSLE患者中重度认知功能损伤的比例更高。通过将认知损伤程度与MoCA进行相关性分析可见MoCA得分可以较好地反映认知功能障碍。NPSLE与对照组相比脑脊液中IL-6、IL-8、IP-10、MMP-9浓度升高。且在鞘内注射地塞米松治疗后有下降趋势。结论NPSLE患者认知功能较健康对照存在明显异常,蒙特利尔认知评估量表较为综合地评估了认知状况,可在临床上作为筛查量表。活动的NPSLE患者中枢神经系统中细胞因子以IL-6增高为主和趋化因子以IL-8和IP-10增高为主,同时还有MMP-9的升高。IL-6和IL-8随治疗有较明显的下降趋势。
[Abstract]:Objective to evaluate the cognitive function of patients with neuropsychiatric lupus (NPSLE) and the changes of biomarkers in cerebrospinal fluid (CSF). To explore an effective clinical evaluation method for neuropsychiatric lupus. Methods the memory, attention, executive function, visual and spatial ability were evaluated by the (VLT), word fluency test, the digit symbol test, the complex figure test, the (CFT) Stroop color word test, the (CWT), connection test, the (TMT), Jack test, and so on. All subjects were screened for cognitive function by the Montreal Cognitive Assessment scale (MoCA) and the hospital anxiety and depression scale was used to evaluate the patients' affective abnormality. Collection and determination of interleukin 6 (IL-6), interleukin 8 (IL-8), interferon gamma inducible protein 10 (IP-10), monocyte chemoattractant protein 1 (MCP-1), mediating activation of normal T cell expression and secretion of (RANTES), macrophage inflammatory protein in cerebrospinal fluid 3 (MIP-3a), matrix metalloproteinase 9 (MMP-9) and interleukin 23 (IL-23). The above indexes were compared between NPSLE patients, patients with systemic lupus erythematosus without neuropsychiatric symptoms and patients with non-autoimmune diseases. Results the cognitive function of NPSLE patients was significantly different from that of the control group in connection test, complex figure copying, digital symbol replacement Stroop color word test and auditory word learning test, which indicated that the cognitive function of NPSLE patients was lower than that of the normal control group in the field of knowledge. The cognitive fields of attention, mental motor speed and word memory were also significantly different from those of lupus patients without neuropsychiatric symptoms. And the proportion of NPSLE patients with moderate and severe cognitive impairment is higher. The correlation analysis between the degree of cognitive impairment and MoCA showed that the MoCA score could reflect the increase of IL-6 / IL-8 / IP-10 / MMP-9 in cerebrospinal fluid (CSF) as compared with the control group. After intrathecal injection of dexamethasone, there was a decreasing trend. Conclusion the cognitive function of NPSLE patients is significantly abnormal than that of healthy controls. The Montreal Cognitive Assessment scale can be used as a screening scale. The cytokines in the central nervous system of active NPSLE patients were mainly increased in IL-6 and chemokines in IL-8 and IP-10. Meanwhile, the increase of MMP-9, IL-6 and IL-8 in the central nervous system showed a significant downward trend with the treatment.
【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R593.24;R747.9

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