CXCL16在小鼠免疫性肝损伤中的作用及意义

目的研究CXCL16的表达对小鼠免疫性肝损伤中的作用及意义。方法建立卡介苗和内毒素诱导的小鼠肝损伤模型，通过实时定量聚合酶链反应和免疫组织化学分析CXCL16在肝组织中的表达变化，根据肝脏病理变化和免疫组织化学结果分析，比较CXCL16的表达水平和肝脏损伤程度的关系。从模型中各个时间点的肝损伤组织中分离浸润单核细胞，计算浸润的细胞数量变化，并进一步分析其中主要的CD4和CD8T淋巴细胞亚群的数量变化，研究CXCL16在肝脏炎症和损伤中的作用和意义。结果成功复制了小鼠免疫性肝损伤模型，发现在肝脏炎症和损伤中CXCL16表达水平显著上调，CXCL16的表达水平与肝脏损伤程度密切相关，肝脏组织浸润的单核细胞数晕明显增加，淋巴细胞尤其是CD4 、CD8 T淋巴细胞数量也有明显的增加。结论小鼠肝脏损伤过程中CXCL16表达水平的增加与肝损伤程度密切相关，CXCL16趋化淋巴细胞浸润可能是导致肝脏损伤的重要机制之。     

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。     

免疫性肝损伤相关细胞因子研究进展

乙型肝炎病毒等多种诱因导致免疫性肝损伤,促成肝细胞的病变的重要因素是免疫应答中产生的细胞因子。本文综述了有关细胞因子与免疫性肝损伤发病机制的实验研究进展。     

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.     

抗IL-18单克隆抗体对小鼠免疫性肝损伤的作用研究

目的探求抗IL-18单克隆抗体对小鼠免疫性肝损伤的作用.方法建造昆明小鼠免疫性肝损伤模型,腹腔注射抗IL-18单克隆抗体,ELISA法测定血清中IL-18、IL-1、TNF-α含量,肝组织HE、Van Gieson染色观察病理组织形态.结果抗IL-18单克隆抗体组明显抑制了IL-18、IL-1、TNF-α的升高(P＜0.05);抗IL-18单克隆抗体组肝脏病理损害均不同程度减轻.结论抗IL-18单克隆抗体能明显减轻免疫性肝损伤小鼠肝脏病理损害,对免疫性肝损伤起到了保护作用.     

急性脑梗死患者血清CXCL16水平与卒中亚型的关系

目的 探讨急性脑梗死患者血清CXCL16水平变化及其与脑梗死TOAST病因学分型之间的关系.方法 应用酶联免疫吸附法检测113例急性脑梗死患者血清CXCL16水平,按TOAST分型进行分组,将各亚组之间以及与32例健康对照者进行比较.结果 病例组血清CXCL16水平显著高于对照组[(2.29±0.21)ng/ml对(1.75±0.21)ng/ml,t=12.863,P=0.000];大动脉粥样硬化性卒中组血清CXCL16水平显著高于小动脉闭塞性卒中组[(2.38±0.23)ng/ml对(2.21±0.11)ng/ml,q=5.743,P=0.000],而且两者均显著高于对照组(q=20.501,P=0.000;q=13.527,P=0.000).在大动脉粥样硬化性卒中组中,≥2条动脉狭窄组血清CXCL16水平与仅有1条动脉狭窄组无显著差异[(2.34±0.24)ng/ml对(2.46±0.19)ng/ml,t=-1.969,P=0.054].多变量logistic回归分析显示,CXCL16(OR=0.972,95% CI 0.956～0.978,P=0.001)和高脂血症(OR=3.547,95% CI1.160～10.848,P=0.020)足脑梗死发生的独立危险因素.结论 血清CXCL16水平在脑梗死急性期升高,与脑梗死发生密切相关,且大动脉粥样硬化性卒中组显著高于小动脉闭塞性卒中组.     

Autoimmune pancreatitis characterized by predominant CD8+ T lymphocyte infiltration

Autoimmune pancreatitis(AIP)is a rare form of pan-creatitis characterized by prominent lymphocyte inf iltration and pancreatic f ibrosis resulting in organ dysfunc-tion.The pathogenesis and pathology of AIP remain unknown.A 64-year-old Chinese man presented with symptoms and signs of bile duct obstruction diffuse enlargement of the head of pancreas,elevated IgG levels,and negative autoimmune antibody responses.A pylorus-preserving pancreatoduodenectomy was per-formed and a pancreatic tumor was suspected.How...     

药物性肝损伤发病机制研究进展

药物的肝脏毒性是欧美国家导致急性肝衰竭的重要原因。Kaplowitz提出的以特异性“上游”事件和非特异性“下游”事件为基础的DILI（Drug induced liver injury，DILI）发病机制，为进一步开展DILI机制的研究提供了明确的方向。目前已知，DILI的发生机制复杂，涉及药物代谢、线粒体功能损伤、免疫反应、信号转导、遗传和环境等多个方面。DILI的发生和进展可能是多重因素综合作用的结果。     

Rapamycin prevents Concanavalin A-induced liver injury by inhibiting lymphocyte activation

Background and Aims:  Liver injury induced by Concanavalin A (Con A) is often used as a model to study the pathophysiology of immune mediated liver injury. Rapamycin (Rapa) is an effective immunosuppressant widely used for preventing immune activation and transplant rejection. However, the effect of Rapa on liver injury caused by Con A has not been carefully examined. In the present study, we examined the effect of Rapa on liver injury caused by Con A.
Methods:  Mice received intraperitoneal Rapa injection before Con A intravenous administration. The liver injury was examined by measuring serum transaminase and pathology, and the level of cytokines was detected by enzyme linked immunosorbent assay (ELISA).
Results:  In the present study, we examined the effect of Rapa on liver injury after Con A injection in mice. We found that the treatment of mice with Rapa protected the liver from Con A-induced injury. Pretreatment with Rapa dramatically ameliorated Con A-induced mortality. This protection was associated with reduced transaminase levels in the blood and further confirmed by liver histology. ELISA showed that Rapa suppressed pro-inflammatory cytokines IFN-γ and TNF-α production as compared with the untreated controls. Furthermore, intrahepatic lymphocyte proliferation was significantly inhibited.
Conclusion:  These findings suggested that Rapa has the therapeutic potential for treatment of immune-mediated liver injury in the clinic.     

辅助性T淋巴细胞17/调节性T淋巴细胞比值失衡在免疫性肝损伤大鼠模型中的变化特点

目的探讨大鼠免疫性肝损伤模型建立的方法以及辅助性T淋巴细胞(Th)17/调节性T淋巴细胞(Treg)失衡在免疫性肝炎大鼠模型中的变化特点。方法采用随机数字表法将30只雌性Wistar大鼠分为3组,每组10只,分别是急性免疫性肝损伤模型(AC)组、慢性免疫性肝损伤模型(CC)组和健康对照(HC)组。AC组和CC组分别通过尾静脉注射α-galcer和刀豆蛋白A(ConA)建立,HC组注射等量的生理盐水。建模成功后检测血清转氨酶ALT、AST等;HE染色观察大鼠肝脏病理改变;免疫组化法检测肝脏中Foxp3、RORγt蛋白表达。外周血和脾脏悬液中Th17、Treg细胞频率变化采用流式细胞分析术检测并计算Th17/Treg比值。计量资料多组间比较采用单因素方差分析,进一步两两比较用SNK-q检验。结果与HC组比较,AC组、CC组血清中ALT、AST、TBil均升高,Alb水平降低,差异均有统计学意义(F值分别为14.782、20.765、16.088、74.181,P值均<0.001)。HE染色,与HC组相比,AC组、CC组分别出现急慢性肝细胞损伤改变。与HC组相比,AC组Th17细胞频率及蛋白(RORγt)水平均显著升高(P值均<0.05),Treg细胞频率亦升高(P<0.05),Th17/Treg比值也显著上升(P<0.05);CC组Th17细胞频率、Treg细胞频率均显著升高,Th17/Treg比值明显下降(P值均<0.05)。结论α-galce及ConA均可成功建立免疫性肝损伤模型,均未出现死亡,肝组织学及血清生化学变化符合急、慢性免疫性肝炎特点。Th17/Treg失衡在炎症反应、组织损伤中发挥了重要作用,且与其免疫状态和病情进展密切相关。     

药物性肝损伤发病机制研究进展

近年来,由于临床药物的不合理应用、保健品及膳食补充剂成分不明确、药物安全知识普及不够等原因,药物性肝损伤(DILI)的病例逐年递增,并成为了肝衰竭及肝移植的重要原因。DILI的发病机制复杂,各医疗机构对DILI的关注度不断提高,其相关性的动物及细胞实验正在全球陆续开展,对其代谢途径、免疫机制、线粒体异常、基因学等方面的研究都取得了不同程度的进展,各种发病机制的深入研究和相互关系的探索,对揭示DILI的真正致病原因具有重大意义。综合了国内外与DILI发病相关的文献,阐述了其发病机制的研究概况,为临床治疗和基础研究提供参考。     

Severity of coronary artery stenosis is associated with a polymorphism in the CXCL16/SR-PSOX gene

OBJECTIVE: Enhanced expression of CXCL16 has been demonstrated in atherosclerotic plaques and several properties have been attributed to CXCL16 that could influence the atherosclerotic process. CXCL16 exists in transmembrane and soluble forms. The transmembrane form acts as a scavenger receptor for oxidised LDL whereas the soluble form acts a chemoattractant for mainly CD8+ T cells. In addition, the soluble form of CXCL16 influences human aortic smooth muscle cell proliferation in vitro. In the present work, a human molecular genetic approach employing a common polymorphism within exon 4 of CXCL16 (181 Ala>Val) was used to investigate whether CXCL16 may be involved in the development of coronary artery disease. The polymorphism is located within the spacer region between the chemokine and transmembrane region and potentially influences an Ala/Val cleavage site, a site commonly used for the release of chemokines by tumour necrosis factor-alpha converting enzyme. DESIGN AND SUBJECTS: We first genotyped 387 unselected survivors of a first myocardial infarction aged <60 years and 387 sex- and age-matched controls. A subset of patients (n = 236) was evaluated by quantitative coronary angiography. Secondly, a cohort of 468 patients undergoing percutaneous transluminal coronary angioplasty (PTCA) with stent implantation was genotyped. RESULTS: No significant difference in allele frequency between patient and controls of the 181 A>V polymorphism was detected. However, the V-allele was associated with increased severity of coronary stenoses. Secondly, the V-allele was associated with smaller minimal luminal diameter in the coronary segment subjected to intervention in a second cohort of patients undergoing PTCA with stent implantation. CONCLUSIONS: The present work provides evidence that CXCL16 is involved in processes leading to enhanced stenosis in atherosclerotic coronary arteries.     

Natural killer T cells in liver injury,inflammation and cancer

The liver is an organ that has the largest amount of natural killer T(NKT) cells, which play critical roles in the pathogenesis of liver diseases. In this article, the authors summarize recent findings about the roles of NKT cells in liver injury, inflammation, fibrosis, regeneration and cancer. In brief, NKT cells accelerate liver injury by producing pro-inflammatory cytokines and directly killing hepatocytes. NKT cells are involved in complex roles in liver fibrogenesis. For instance, NKT cells inhibit liver fibrosis via suppressing hepatic stellate cell activation and can also promote liver fibrosis via enhancing liver inflammation and injury. Inactivated or weakly activated NKT cells play a minimal role in controlling liver regeneration, whilst activated NKT cells have an inhibitory effect on liver regeneration. In liver cancer, NKT cells play both pro-tumor and anti-tumor roles in controlling tumor progress.     

二草清肝汤抗大鼠免疫性肝损伤作用机制的研究

目的：观察中药二草清肝汤对大鼠免疫性肝损伤的防护作用并探讨其药理学机削。方法：采用卡介苗（BCG）＋脂多糖（LPS）建立大鼠免疫性肝损伤模型。做肝组织病理切片观察肝组织损伤情况；采用免疫组化法检测肝组织Bax、Bcl-2的表达；ELISA法检测血清IL-12水平。结果：大鼠免疫性肝损伤时。血清IL-12水平显著升高；肝脏Bax表达明显升高，Bcl-2表达显著降低；中药组及西药（环磷酰胺）对照组大鼠Bax的表达及IL-12水平明显低于模型组（P〈0．01），而Bcl-2表达明显高于模型组（P〈0．01）；中药组和西药组大鼠肝组织病理改变较模型组明显减轻。中药组一般情况明显好于西药组。结论：二草清肝汤能降低免疫性肝损伤大鼠的血清IL-12水平，下调肝Bax的表达。上调Bcl-2的表达，对实验性免疫性肝损伤有明显防护作用。     

细胞因子及其信号通路在放射性肝损伤发病中的作用研究进展

放射性肝损伤（radiation-induced liver injury,RILI）是原发性肝癌及其他腹腔肿瘤放射治疗中最主要的并发症之一,它制约了肿瘤区的放疗剂量,严重影响了患者的治疗疗效。研究发现RILI的发生与多种细胞因子相关。细胞因子通过启动多种下游信号通路参与RILI各阶段的发病。     

药物淋巴细胞刺激试验在药物性肝损伤诊断中的意义

目的评估药物淋巴细胞刺激试验(drug lymphocyte stimulation test,DLST)对药物性肝损伤(Drug induced liver injury,DILI)临床诊断的意义。方法对84例临床诊断为DILI、17例疑诊、17例有服药史的非DILI患者行DLST检测,结合其人口学资料、临床分型、临床生化指标等进行非随机对照的回顾性分析,进一步评价DLST在临床的应用价值。结果 101例临床诊断或疑诊DILI患者中,共36例DLST阳性,DLST特异度为98.6%,在所有DILI患者中(包括过敏特异质和遗传特异质)敏感度35.6%。DLST阳性与RUCAM有较好的相关性(P=0.015)。结论药物淋巴细胞刺激试验对药物导致的肝损伤具有较高的诊断特异性,结合RUCAM评分可提高DILI的诊断标准性。     

Vitamin D3 modulates T lymphocyte responses in hepatitis C virus-infected liver transplant recipients

Background

Aim of the present study was to investigate whether 1,25(OH)(2)D(3) (Vitamin D3) modulates T lymphocyte functions in patients transplanted for hepatitis C virus-related cirrhosis.

Methods

Sixteen patients and ten healthy subjects were investigated. T lymphocytes were activated in vitro in the presence or absence of Vitamin D3 and then the proliferative response and IFN-γ and TNF-α production were assessed.

Results

Vitamin D3 potently reduced T-lymphocyte proliferation in a dose-related fashion. Similarly, FACS analysis and ELISA testing demonstrated that Vitamin D3 significantly decreased the response frequency and the response intensity of IFN-γ and TNF-α production in the whole CD3-positive T lymphocyte population as well as in “naive” CD4+ CD45RA+ and “memory” CD4+ CD45RO+ T lymphocyte subsets. The inhibitory effect of Vitamin D3 on T-cell proliferation and cytokine production was not different between patients and controls. No toxic effects were exerted by Vitamin D3 even at the higher concentration used (10 nM). Finally, no statistically significant correlation was found between 25(OH)D serum levels and the proliferative response or cytokine production of T lymphocytes from transplanted patients.

Conclusions

This study demonstrates that in patients transplanted for hepatitis C virus-related cirrhosis Vitamin D3 modulates T lymphocyte activation, and provides a rationale for the evaluation of this compound as an immunosuppressive agent in liver-transplanted patients.     

LDH法检测pcDNA-HPV16L1免疫小鼠CTL活性的研究

目的观察pcDNA—HPV16L1免疫BALB／c小鼠细胞毒性T细胞（CTL）活性变化,建立简便易行的CTL检测体系,为人乳头瘤病毒（HPV）疫苗免疫中CTL作用的研究奠定基础。方法用pcDNA—HPV16L1转染的小鼠黑色素瘤B16细胞作为靶细胞,用pcDNA—HPV16L1免疫BALB／c小鼠（观察组）并以乳酸脱氢酶（LDH）法检测其CTL活性,设空质粒组与空白组作为对照（分别肌注空质粒和葡萄糖）。结果与空质粒组和空白组比较,观察组CTL活性显著增强。结论pcDNA—HPV16L1免疫小鼠的CTL活性增强,LDH法可稳定检测。     

老年肺心病急性期患者免疫功能的分析

目的:研究老年肺心病患者T淋巴细胞亚群的变化,并探讨其与急性期和缓解期的关系。方法:用CD系列抗人T淋巴细胞克隆抗体和流式细胞仪技术测定40例老年肺心病急性期和缓解期患者外周血T淋巴细胞亚群,并与22例老年健康对照组作比较。结果:老年肺心病急性期CD4/CD8低于老年健康对照组（1.16±0.53:1.43±0.25,P<0.05）;缓解期CD4/CD8（1.36±0.45）高于急性期组（1.16±0.53,P<0.05）。结论:老年肺心病患者在急性期免疫功能降低,随着病情的缓解免疫功能得到改善。