慢性丙型肝炎患者血清趋化因子CXCL9和CXCL11的检测及其临床意义

目的探讨慢性丙型肝炎患者血清趋化因子CXCL9和CXCL11的变化规律及其临床意义。方法用酶联免疫吸附法（ELISA）检测血清CXCL9和CXCL11的浓度;荧光定量反转录聚合酶链反应法（RT-PCR）检测HCVRNA病毒载量;INNO-LiPA线性探针杂交法检测HCV基因分型;全自动生化分析仪检测肝功能。结果对照组（n=26）和慢性丙型肝炎组（n=48）血清CXCL9的浓度分别为（596．8±238．4）pg／mL和（2457．8±1650．7）pg／mL,血清CXCL11的浓度分别为（106．8±76．95）pg／mL和（307．54-259．4）pg／mL,差异均具有统计学意义（P〈0．05）。在慢性丙型肝炎组内,CXCL9和CXCL11的水平在不同HCV1b基因型组和2a基因型组之间无显著差异。CXCL9和CXCL11浓度与血清ALT水平无相关性（CXCL9：r=-0．119,P=0．397;CXCL11：r=0．219,P=0．138）,与HCVRNA载量也无相关性（CXCL9：r=0．253,P=0．212;CXCL11：r=0．105,P=0．451）。结论CXCL9和CXCL11可能参与了慢性丙型肝炎感染导致的肝脏免疫损伤过程,ALT和HCVRNA与CXCL9和CXCL11浓度变化无明显相关性。     

乙型肝炎患者血清趋化因子CXCL16的检测及其意义

目的 探讨乙肝患者血清趋化因子CXCL16的变化规律及其临床意义.方法 用酶联免疫吸附法(ELISA)检测血清CXCL16浓度;荧光定量聚合酶链反应法(FQ-PCR)检测HBV-DNA;全自动生化仪检测肝功能.结果 对照组(n=25)、急性乙肝组(n=24)、慢性乙肝组(n=32)CXCL16浓度分别为1.676±0.766(ng/nd)、2.150±0.714(ng/ml)、2.417±0.537(ng/ml).急、慢性乙肝组CXCL16浓度显著高于对照组(P值分别为0.015、0.000).急、慢性乙肝组之间比较,差异无统计学意义(P=0.142).HBeAg阳性乙肝组(n=26)与HBeAg阴性乙肝组(n=30)比较,差异无统计学意义(P=0.741).CXCL16浓度与ALT水平无相关性(r=-0.46,P=0.736),与HBVDNA拷贝数也无相关性(r=-0.191,P=0.158),但CXCL16有随病情加重而增高的趋势.结论 CXCL16可能参与了乙肝的炎症损伤机制;ALT、HBVDNA及HBeAg与CXCL16浓度变化无明显相关.     

CXCL10和CXCL16在胶原诱导性关节炎大鼠外周血中的测定及意义

目的探讨趋化因子CXCL10和CXCL16在Ⅱ型胶原诱导性关节炎（C IA）发病中的作用。方法随机选取10只雌性近交系Lewis大鼠注射Ⅱ型胶原建立C IA动物模型,10只仅注射生理盐水的同类大鼠为对照,在注射后第10天、第3周、第6周和第9周采用ELISA法分别检测CXCL10和CXCL16的血清水平,计算大鼠的关节炎症指数,分析相关性。结果Ⅱ型胶原注射后大鼠的CXCL10和CXCL16血清水平均随时间的延长和关节指数的增高而增高,第9周达高峰。与正常对照组相比,第6周和第9周的CIA组大鼠外周血CXCL10及CXCL16水平均增高（P〈0.05或0.01）。血清CXCL10水平与CXCL16水平呈正相关。CIA组大鼠血清CXCL10及CXCL16水平与关节炎症指数均呈正相关。结论 CIA大鼠血清CXCL10及CXCL16水平升高与关节炎活动性相关;CXCL10及CXCL16在CIA发病过程中可能发挥了重要而协同的作用。     

趋化因子CXCL11在急性坏死性胰腺炎大鼠胰腺组织的表达及其作用

目的 观察趋化因子CXCL11在急性坏死性胰腺炎(ANP)病程中的动态变化,探讨其在ANP发病过程中的作用.方法 48只SD大鼠按数字表法随机分为对照组和ANP组,每组24只.采用4％牛黄胆酸钠(1 ml/kg体重)逆行胰胆管注射方法制备ANP大鼠模型.术后1、3、6、12 h处死大鼠,留取标本.检测血清淀粉酶活性,胰腺组织行常规病理检查并评分,免疫组化法检测胰腺组织CXCL11表达,定量PCR法检测胰腺组织CXCL11 mRNA表达,酶联免疫吸附试验法检测血清CXCL11水平.结果 ANP组大鼠血清淀粉酶活性较对照组显著升高[6h时为(6153±355)U/L比(185±32)U/L,P＜0.05]；胰腺病理损伤明显,病理评分较对照组显著增加[6h时为(9.00±0.63)分比(0.33±0.12)分,P＜0.05]；胰腺组织CXCL11 mRNA及蛋白表达较对照组显著增强(6h时为3.13±0.43比0.99±0.24,2.76±0.27比0.33±0.12,P值均＜0.05)；血清CXCL11水平较对照组明显升高[6h时为(112.1±14.2)ng/L比(56.8 4.3) ng/L,P＜0.05].结论 CXCL11是急性胰腺炎早期的炎症介质,参与了大鼠ANP的发病过程.     

趋化因子CXCL10在心脏疾病中的研究进展

趋化因子是一类具有诱导细胞定向移动属性的促炎细胞因子,其受体是一组G耦联蛋白。趋化因子的分子中含有 4 个保守的半胱氨酸 (C),依据半胱氨酸的序列位置位置将其分为C、CC、CXC、CXXXC四大类。CXC类中的CXC趋化因子配体10(chemokine ligand一10,CXCLl0)又称干扰素诱导蛋白(interferon-y-inducible protein 10,IP一10),在调节免疫应答、细胞增殖、血管生成等过程中起了重要作用[1]。近年来有大量研究表明,CXCL10与免疫性脑脊髓炎、克罗恩病、肺结核、甲状腺疾病、I型糖尿病和肿瘤等疾病的发生、发展及预后均有相关性[2]。最近有多个研究显示证据,CXCL10和多种心脏疾病有密切联系。     

慢性重型乙型肝炎患者血清趋化因子RANTES与MIG水平检测及其意义

目的：了解慢性重型乙型肝炎（简称慢重肝）患者血清趋化因子调节激活正常T细胞表达的分泌的细胞因子（RANTES）、γ-干扰素诱生的单核因子（MIG）水平,并探讨患者血清RANTES、MIG水平与丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、总胆红素（TBil）、凝血酶原活动度（PTA）及乙型肝炎病毒脱氧核糖核酸（HBVDNA）载量的相关性。方法：运用双抗体夹心酶联免疫吸附法检测23例慢重肝患者（肝炎组）和14名健康人（正常对照组）血清中趋化因子RANTES、MIG的浓度,并与患者的肝功能生化指标、HBV DNA载量进行相关性分析,利用SPSS 11.5软件进行统计分析。结果：慢重肝患者血清RANTES浓度[（288.52±54.96）ng/ml]低于正常对照组[（456.77±20.34）ng/ml],其差异有显著性意义（P〈0.05）;慢重肝患者血清MIG浓度[（91.49±18.71）ng/ml]高于正常对照组[（11.43±1.44）ng/ml],其差异有显著性意义（P〈0.05）;MIG水平与AST、ALT呈正相关,与TBil、PTA、HBV DNA无明显相关。结论：慢性重型乙型肝炎患者血清RANTES水平降低,MIG水平增高;RANTES水平不能反映肝细胞坏死程度,MIG参与肝脏炎性细胞浸润,介导肝组织损伤,可能参与重型肝炎发病机制。     

趋化因子CXCL10(IP-10)/CXCR3在类风湿关节炎发病中的作用及应用前景

类风湿关节炎（RA）是一类以关节炎为主要临床表现的系统性自身免疫性疾病。实验证明,T细胞尤其是CD4~＋T细胞的异常活化及其分泌的细胞因子所形成的网络参与了RA激发和延续。趋化因子在炎症细胞向滑膜组织迁移及活化过程中发挥了关键作用,趋化因子C-X-C配体10/干扰素诱导蛋白-10（CXCL10/IP-10）可与表达在T细胞表面的受体趋化因子C-X-C受体3（CXCR3）结合促进其活化并向CD4~＋Th1细胞方向分化,从而促进炎症反应。研究发现,CXCL10在RA血清及滑膜中表达增高。目前作为RA的一个可能的致病因素,CXCL10/CXCR3在发病机制中的作用越来越受到重视。研究发现,CXCL10抗体及裸DNA疫苗可对RA关节炎有抑制及治疗作用,其可能作为RA治疗新靶点的研究日益增多。     

细胞趋化因子受体CXCR3及CCR5在乙型肝炎患者肝组织中的表达

通过测定急性和慢性乙型肝炎患者肝内细胞趋化因子受体(CCR5)和CXCR3水平,结合患者血中乙型肝炎病毒(HBV)含量,探讨趋化因子受体在乙型肝炎发病及其转归中的作用。1.材料与方法:(1)试剂:链霉素抗生物素蛋白过氧化酶免疫染色超敏试剂盒,兔抗CCR5和CXCR3单克隆抗体,抗体效价1:500.均购自深圳华氏试剂公司,按试剂盒说明书进行操作。(2)病例:大连市第六人民医院2002年1月至2003年     

e抗原阳性慢性乙型肝炎患者外周血树突状细胞Toll样受体3的表达及意义

目的探讨Toll样受体3（TLR3）的表达与HBV感染后宿主免疫清除障碍的关系。方法选取轻度CHB患者50例,健康对照者48名,其外周血用免疫磁珠细胞分选法获得纯化的CD14^＋单核细胞,用RPMI 1640培养基培养,并且用人粒细胞-巨噬细胞集落刺激因子和hIL-4诱导单核细胞成为未成熟的髓样树突状细胞（mDC）,加入聚肌胞刺激后获得成熟的mDC。分别在剌激后0、12、24、48h用流式细胞仪检测TLR3、CD86、HLA-DR和CD1a的表达,实时PCR检测TLR3的表达变化。结果健康对照组中mDC在刺激后24h,TLR3表达较0 h时上调显著（P〈0.05）,48h时TLR3的表达与0h相比差异无统计学意义（P〉0.05）;患者组在刺激后12、24h TLR3的表达与0h时相比,上调不明显,48h时TLR3的表达显著上调（P〈0.05）。实时PCR检测mDC上TLR3 mRNA结果发现,对照组TLR3 mRNA在刺激后12h的表达水平较0h显著上升（P〈0.05）,也显著高于患者组刺激后0、12、24h的表达水平;患者组刺激后48h的TLR3 mRNA表达水平较0h显著上升（P〈0.05）。与0h比较,健康对照组在刺激后12、24h和48h,CD86的表达水平显著高于患者组（P〈0.05）。患者组与对照组间CD1a和HLA-DR的表达差异无统计学意义。结论慢性HBV感染者mDC受聚肌胞刺激后TLR3表达异常,协同刺激因子CD86表达低下,可能造成宿主对HBV感染的免疫清除障碍,导致疾病慢性化。     

趋化因子IP-10在慢性乙肝患者血清中的表达及意义

为探讨趋化因子IP-10在慢性乙肝患者的表达水平及其与肝细胞受损程度之间的关系，分别设立健康对照组，慢性乙肝中轻度组、重度组、慢性重型肝炎组，采用ELISA方法检测IP—10、γ-IFN的血清浓度。并同时作常规生化检测。结果慢性乙肝各组IP-10水平均高于对照组，且与ALT、AST呈正相关。表明慢性乙肝患者血清IP-10水平可反映肝细胞损伤程度。     

Circulating CXCL11 and CXCL10 are increased in hepatitis C-associated cryoglobulinemia in the presence of autoimmune thyroiditis

Abstract

Objective No data are available about circulating levels of the CXCL11 chemokine in hepatitis C virus (HCV)-associated mixed cryoglobulinemia (MC) patients with or without autoimmune thyroiditis (AT). The aim of the present study, therefore, was to evaluate serum CXCL11 levels in these patients.

Design Serum CXCL11 (and for comparison, CXCL10) was measured in 45 patients with MC, 45 patients with MC and AT (MC + AT), 45 sex- and age-matched controls without AT (control 1), 45 sex- and age-matched patients with AT without cryoglobulinemia (control 2), and in 45 sex- and age-matched patients with hepatitis C chronic infection without MC (HCV+).

Results Serum CXCL11 and CXCL10 levels were significantly higher in control 2 than in control 1 (p < 0.01). MC patients had CXCL11 and CXCL10 significantly higher than control 1 (p < 0.01). MC + AT patients had CXCL11 and CXCL10 higher than control 2 (p < 0.01) and MC patients (p = 0.02). Serum CXCL11 levels were not associated with any of the clinical features of cryoglobulinemia in patients with MC and MC + AT, which was the same for CXCL10. CXCL10 and CXCL11 in HCV+ patients were significantly higher than in controls 1 and 2, but lower than in MC or MC+AT patients.

Conclusion Our study first demonstrates higher serum levels of CXCL11 chemokine in patients with MC than in HCV+ patients, and in particular in the presence of AT.     

慢性肝病患者乙肝病毒血清学标志物转换规律及其意义

目的探讨乙肝病毒血清学标志物（HBVM）在慢性肝病患者中的转换规律及临床意义。方法选择慢性肝病患者包括慢性病毒性乙型肝炎、慢性重型乙型肝炎、肝炎肝硬化和原发性肝癌患者183例,采用ELISA方法对HBVM（HBsAg、HBsAb、HBeAg、HBeAb和HBcAb）进行检测,采用荧光定量聚酶链反应法进行HBV DNA检测,将HBV DNA检测值进行对数转换行统计学分析。结果慢性肝病患者的HBVM共有3种模式：大三阳（L3PP：HB-sAg、HBeAg和HBcAb）、小三阳（S3PP：HBsAg、HBeAb和HBcAb）和小二阳（S2PP：HBsAg和HBcAb）。L3PP HBVDNA水平高于S3PP和S2PP（P〈0.01）。随着慢性肝病病情发展,L3PP阳性率呈下降趋势,S3PP和S2PP阳性率呈上升趋势（P均〈0.01）;不同临床类型的慢性肝病患者3种HBVM模式的分布存在统计学差异（P〈0.01）。结论 L3PP慢性肝病患者HBV DNA复制水平高于S3PP或S2PP模式。随着慢性肝病病情的进展,HBVM的模式可发生转换,HBeAg阴转,L2PP转为S3PP或S2PP。     

Analysis of differential gene expression between chronic hepatitis B patients and asymptomatic hepatitis B carriers

BACKGROUND AND AIMS: Chronic hepatitis B virus (HBV) infection remains a serious global health problem, inducing a spectrum of diseases, including asymptomatic HBV carriage (ASC) and chronic hepatitis B (CHB). ASC and CHB represent different immunological states and their prognoses are diverse. To clarify molecular mechanisms underlying the two infection states, the differentially expressed genes between the two states were screened and identified. METHODS: Subtracted complementary DNA libraries by suppression subtractive hybridization, dot blot hybridization and quantitative real-time PCR were used to identify the differentially expressed genes between subjects with CHB and those with ASC. RESULTS: RNA from peripheral blood mononuclear cells from CHB and ASC subjects was subjected to suppression subtractive hybridization and resulted in isolation of subtracted complementary DNA clones. Eighty-eight randomly sampled clones were rescreened by dot blot hybridization, from which 29 clones were identified as differentially expressed genes. The differential expression of three genes was confirmed by real-time PCR in 23 subjects with CHB and 21 with ASC. CONCLUSIONS: Differentially expressed genes in peripheral blood mononuclear cells between CHB and ASC have been isolated by suppression subtractive hybridization, including some new genes. Of the up-regulated genes in CHB, most are known to be responsive to inflammatory conditions. These genes might provide clues in elucidating the mechanisms of the two different HBV infection states and designing therapeutic targets for HBV infection.     

Predictive significance of CXCL8, CXCL10 and CXCL16 in juvenile idiopathic and rheumatoid arthritis Iraqi patients

Aim of the workTo evaluate the predicative significance of three chemokines (CXCL8, CXCL10 and CXCL16) in juvenile idiopathic arthritis (JIA) and rheumatoid arthritis (RA) and to focus on their relation to some laboratory findings and clinical features.Patients and methodsSerum level of the chemokines was determined in 79 JIA and 77 RA Iraqi patients, as well as their matching controls by enzyme linked immunosorbent assay.ResultsJIA and RA patients shared significant increase of CXCL8 (24 vs. 18 and 37 vs. 15 pg/ml) and CXCL10 (38.5 vs. 17.1 and 41.5 vs. 13.2 pg/ml, respectively) compared to their controls, while no such variation observed in CXCL16 level. Regression analysis revealed that both CXCL8 and CXCL10 were significant risk factors in JIA and RA. Only rheumatoid factor-seropositive RA patients had a significantly higher CXCL10 (43 vs. 32; p = 0.014) and CXCL16 (21.2 vs. 17.7; p = 0.003) level compared seronegative patients. The CXCL10 at a cut-off value of 29.2 pg/ml in JIA showed a sensitivity of 91.1% and specificity of 91.8% and at 20.1 pg/ml in RA reached 100% and 96.2%, respectively. CXCL8 in JIA showed a sensitivity of 74.7% and specificity of 72.6% at18.6 pg/ml and in RA were 93.5% and 79.7%, respectively at 21.2 pg/ml.ConclusionsCXCL8 and CXCL10 are potential predictors of JIA and RA. CXCL10 is a more significant predictor. The CXCL16 was not found to have such impact and it might be of value in a subgroup of seropositive RA patients.     

白细胞介素10对慢性乙型肝炎患者自然杀伤细胞的调控作用

目前治疗手段难以彻底治愈慢性乙型肝炎(CHB)。自然杀伤细胞(NK细胞)是天然免疫的一个重要组成部分,在机体免疫监视和早期抗感染免疫过程中起重要作用。白细胞介素10(IL-10)是一种多功能负性调节因子,参与免疫细胞和炎症细胞等的生物调节。介绍了IL-10和NK细胞的特点及功能,CHB与IL-10和NK细胞的关系,以及IL-10和NK细胞在CHB治疗中的意义,认为在CHB中IL-10可能发挥了负性调控NK细胞功能的作用,但是能否通过阻断IL-10对NK细胞的调控作用提高NK细胞的抗病毒功能,同时避免NK细胞激活造成的肝脏免疫病理,仍有待进一步研究。     

HBV慢性感染者和非感染者IL-10启动子基因多态性比较

目的探讨IL-10启动子基因多态性对HBV感染者易感性和慢性化的影响。方法选择52例慢性乙型肝炎患者为观察对象,采用限制性长片段多肽分析和直接测序的方法,检测IL-10启动子基因多态性,并与48例健康人群基因分布频率进行比较。结果从等位基因单基因分布频率分析比较,病毒携带者和健康人群组分布频率无显著统计学差异;从基因型分布频率比较两者间无显著差异;从单倍体分析,两组间比较也无明显差异。无论是HBV慢性感染者还是健康人群在-1082位的等位基因A和-819位的等位基因T有较高的分布频率。结论 IL-10启动子基因多态性可能对HBV易感性和慢性化无显著影响。