【摘要】：目的評估神經精神狼瘡(NPSLE)患者認知功能情況及其腦脊液(CSF)中生物標志物的變化,研究患者認知功能障礙的模式。探索神經精神狼瘡的有效的臨床評估方法。方法通過詞語學習量表(VLT)、詞語流暢性測驗、數字符號測驗、復雜圖形測驗(CFT)、Stroop色詞測驗(CWT)、連線測驗(TMT)、插孔試驗等神經心理量表評估記憶、注意力、執(zhí)行功能、視空間能力、運動及精神運動速度等認知領域并且通過蒙特利爾認知評估量表(MoCA)對所有受試者進行認知功能篩查；同時使用醫(yī)院焦慮抑郁量表對患者進行情感異常方面的評估。收集和測定患者腦脊液中的白細胞介素6(IL-6)、白細胞介素8(IL-8)、干擾素伽馬誘導蛋白10(IP-10)、單核細胞化學趨化蛋白1(MCP-1)、調解活化正常T細胞表達和分泌因子(RANTES)、巨噬細胞炎性蛋白3(MIP-3a)、基質金屬蛋白酶9(MMP-9)、白細胞介素23(IL-23)的濃度。比較上述指標在NPSLE患者、無神經精神癥狀的系統(tǒng)性紅斑狼瘡患者及非自身免疫性疾病患者間的差異。結果NPSLE患者的認知功能在連線測驗,復雜圖形臨摹,數字符號替換、Stroop色詞測驗和聽覺詞語學習測驗中與對照組相比有顯著性差異,提示在知領域均低于正常對照組,其中注意力、精神運動速度及詞語記憶這幾個認知領域與無神經精神癥狀的狼瘡患者也有顯著差異。并且NPSLE患者中重度認知功能損傷的比例更高。通過將認知損傷程度與MoCA進行相關性分析可見MoCA得分可以較好地反映認知功能障礙。NPSLE與對照組相比腦脊液中IL-6、IL-8、IP-10、MMP-9濃度升高。且在鞘內注射地塞米松治療后有下降趨勢。結論NPSLE患者認知功能較健康對照存在明顯異常,蒙特利爾認知評估量表較為綜合地評估了認知狀況,可在臨床上作為篩查量表�；顒拥腘PSLE患者中樞神經系統(tǒng)中細胞因子以IL-6增高為主和趨化因子以IL-8和IP-10增高為主,同時還有MMP-9的升高。IL-6和IL-8隨治療有較明顯的下降趨勢。
[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.
【學位授予單位】：北京協(xié)和醫(yī)學院
【學位級別】：博士
【學位授予年份】：2014
【分類號】：R593.24;R747.9

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