癡呆患者血清和腦脊液中炎前和抗炎細(xì)胞因子的變化

1、    癡呆患者血清和腦脊液中炎前和抗炎細(xì)胞因子的變化            作者：時(shí)間：2007-11-22 11:38:00                           

2、;                          作者：李龍宣，趙斌，許志恩，邢孔鴦，唐榮華【關(guān)鍵詞】  癡呆；白介素1；白介素6；腫瘤壞死因子；白介素1受體拮抗劑Changes of pro and antiinflammatory cytokines in serum and cerebrospinal fluid of pati

3、ents with different kinds of dementias【Abstract】 AIM: To observe the serum and cerebrospinal fluid (CSF) levels of the proinflammatory cytokines, interleukin1 (IL1), interleukin6 (IL6), tumor necrosis factor (TNF), and the antiinflammatory cytokine, interleukin1 receptor antagonist (IL1ra) in patien

4、ts with different kinds of dementias and normal controls and to investigate their clinical meanings. METHODS: A total of 70 cases of patients with different kinds of dementias at the Department of Neurology in our hospital and Peoples Hospital of Taishan City from September 2003 to August 2005 were

5、consecutively selected as the observed subjects, including 30 Alzheimers disease (AD) patients, 15 mixed dementia (MD) patients and 25 vascular dementia (VD) patients. The serum and CSF levels of IL1, IL6, TNF and IL1ra in the patients with different kinds of dementias and the controls were measured

6、 using ELISA. RESULTS: Compared to the controls, the levels of TNF in CSF in the patients with different kinds of dementias were upregulated, whereas the level of IL1ra was downregulated to some extent (P<0.05 or P<0.01). The differences between the CSF levels of IL1 but not of IL6 in the pati

7、ents with AD and those in the controls reached statistical significance (P<0.05). In contrast, the patients with VD displayed significantly higher CSF levels of IL6 but not of IL1 compared to the controls (P<0.05). The CSF levels of IL1 and IL6 in the patients with MD are both significantly hi

8、gher than those in the controls (P<0.01). However, serum levels of IL1, IL6, TNF and IL1ra were not significantly different in the patients with different kinds of dementias in comparison with the controls. No correlations were found between CSF and serum levels of the cytokines. CONCLUSION: The

9、changes of pro and antiinflammatory cytokines in the brain might be the factors of the neuropathological damage in AD, VD and MD.【Keywords】 dementia; interleukin1; interleukin6; interleukin1 receptor antagonist; tumor necrosis factor 【摘要】 目的：研究炎前和抗炎細(xì)胞因子在不同癡呆患者血清和腦脊液中的變化并探討其臨床意義. 方法：200309/200508我院和臺(tái)

10、山市人民醫(yī)院神經(jīng)科就診的70例老年癡呆患者作為觀察對(duì)象，其中阿爾茨海默病（AD）30例、混合性癡呆（MD）15例、血管性癡呆（VD）25例. 用夾心式酶聯(lián)免疫吸附法測(cè)定各組老年人血清和腦脊液中白介素1（IL1），白介素6（IL6），腫瘤壞死因子（TNF）和白介素1受體拮抗劑（IL1ra）的水平. 結(jié)果：各癡呆組患者腦脊液中TNF的水平較正常老年人有不同程度升高，而IL1ra則不同程度降低（P<0.05或P<0.01）；AD組患者腦脊液中IL1水平高于對(duì)照組（P<0.05），IL6含量較對(duì)照組卻無增高；VD組患者腦脊液中IL6水平雖顯著高于對(duì)照組（P<0.05），但I(xiàn)L1

11、含量與對(duì)照組相比無增高； MD組患者IL1，IL6水平較對(duì)照組均有增高（P<0.01）. 各癡呆組血清中IL1，IL6，TNF和IL1ra的水平與正常老年人相比無差異. 相關(guān)分析顯示不同癡呆患者血清與其相對(duì)應(yīng)的腦脊液中炎前和抗炎細(xì)胞因子水平之間無相關(guān). 結(jié)論：癡呆患者腦內(nèi)炎前和抗炎細(xì)胞因子的變化可能是其神經(jīng)病理損害因素.【關(guān)鍵詞】 癡呆；白介素1；白介素6；腫瘤壞死因子；白介素1受體拮抗劑0引言目前人們普遍公認(rèn)，炎性細(xì)胞因子參與阿爾茨海默病（Alzheimers disease, AD）患者腦內(nèi)的神經(jīng)病理損傷過程，并在這方面作了大量的研究工作. 但同時(shí)研究處于不同老年期癡呆患者生前腦內(nèi)炎

12、前和抗炎細(xì)胞因子表達(dá)的報(bào)道罕見. 本文系統(tǒng)研究了不同老年期癡呆患者，包括AD，血管性癡呆（vascular dementia, VD），混合性癡呆（mixed dementia, MD）患者血清與腦脊液（cerebrospinal fluid, CSF）中炎前和抗炎細(xì)胞因子的變化，現(xiàn)報(bào)道如下.1對(duì)象和方法1.1對(duì)象200309/200508我院和臺(tái)山市人民醫(yī)院神經(jīng)科住院患者. 簡(jiǎn)易精神狀態(tài)檢查量表（MMSE）<24分初篩有癡呆納入觀察對(duì)象，按照美國(guó)精神疾病診斷及統(tǒng)計(jì)手冊(cè)第四版（DSM）標(biāo)準(zhǔn)診斷癡呆. AD組30例，均符合美國(guó)神經(jīng)病學(xué)、語言障礙和卒中阿爾茨海默病和相關(guān)疾病學(xué)會(huì)（NINCDS

13、ADRDA）很可能AD的診斷標(biāo)準(zhǔn)，其中男13例，女17例，年齡64.6±7.9（5776）歲，受教育（6.4±4.0）年，MMSE評(píng)分16.2±6.2，Hachinski缺血指數(shù)<4分；MD組15例，診斷根據(jù)有癡呆癥狀，有腦血管病危險(xiǎn)因素，神經(jīng)局灶體征不明顯，MRI示腦內(nèi)無大的梗死，但有小的腔梗，而且數(shù)量在5個(gè)以上(肉眼可見)，其中男8例，女7例，年齡61.8±8.2（5674）歲，受教育（6.4±4.0）年，MMSE評(píng)分16.8±6.4，Hachinski缺血指數(shù)47分；VD組25例，均符合美國(guó)國(guó)立神經(jīng)病與卒中研究所/瑞士神經(jīng)

14、科學(xué)國(guó)際協(xié)會(huì)（NINDSAIREN）很可能VD的診斷標(biāo)準(zhǔn)，其中男14例，女11例，年齡65.3±8.8（4875）歲，受教育（6.5±4.1）年，MMSE評(píng)分16.6±6.4，Hachinski缺血指數(shù)>7分；同時(shí)選取20例老年健康志愿者作為對(duì)照，無記憶障礙和其他癡呆癥狀，其中男11例，女9例，年齡61.0±7.6（5872）歲，受教育（6.5±4.2）年. 各組在性別構(gòu)成、年齡、受教育年限方面無統(tǒng)計(jì)學(xué)差異，各癡呆組患者M(jìn)MSE評(píng)分無統(tǒng)計(jì)學(xué)差異，具有可比性. AD, MD與VD各組患者都有頭顱MRI資料，并詳細(xì)進(jìn)行神經(jīng)系統(tǒng)體查以助于鑒別，

15、同時(shí)除外引起智能障礙的其他原因.上述研究對(duì)象和對(duì)照組均無其他神經(jīng)系統(tǒng)疾病、免疫系統(tǒng)疾病、系統(tǒng)感染（檢查前2 wk無明確感染史）及肝腎功能不全者，且未應(yīng)用精神抑制藥物、非甾體類消炎藥、抗氧化劑及免疫抑制治療. 病例為隨機(jī)選擇，無血緣關(guān)系.1.2方法清晨空腹采集受檢者靜脈血5 mL，離心取血清；并于上午9:0011:00在安靜狀態(tài)下按常規(guī)行腰穿取CSF 23 mL，經(jīng)離心（3500 r/min, 15 min）后，取上清，分裝，置-70保存待測(cè). 血清與腦脊液中炎前細(xì)胞因子白介素1 (IL1)，白介素6（IL6），腫瘤壞死因子 (TNF)和抗炎細(xì)胞因子白介素1受體拮抗劑（IL1ra）用夾心式酶聯(lián)免疫吸附法（ELISA）定量檢測(cè)，試劑盒購(gòu)自晶美生物工程有限公司.統(tǒng)計(jì)學(xué)分析：計(jì)量數(shù)據(jù)以x±s表示, 采用SPSS 12.0軟件進(jìn)行方差分析（F檢驗(yàn)）和多重比較（q檢驗(yàn)）以及直線相關(guān)