肝硬化患者外周血白细胞介素2活性及其与γ干扰素活性的关系

白细胞介素2(IL-2)和γ干扰素(IFN-γ)是T淋巴细胞产生的淋巴因子,在机体的免疫调节和抗肿瘤免疫中发挥着重要作用。我们检测了肝硬化患者和正常人外周血单个核细胞(PBMC)在体外经PHA诱生产生的IL2和IFN-γ活性,结果表明,肝硬化患者IL-2和IFN-γ活性均显著低于对照组(p<0.01),肝硬化组和对照组的IL-2及IFN-γ活性之间均呈直线正相关。细胞免疫功能低下可能是肝硬化患者易并发SBP等感染的原因之一。临床应用IL-2和IFN-γ可能有助于增强和调节患者的细胞免疫功能。     

IL-18与脓毒症关系的研究进展

脓毒症是重症监护室常见的危重症,其病死率高,预后差,诊疗困难。白细胞介素18(IL-18)是一种多效促炎性细胞因子,在脓毒症患者中呈高表达,并可通过炎症级联反应,参与脓毒症的发生发展。该文就IL-18的结构、生物学特性、基因多态性和其在脓毒症中的作用机制进行综述。     

肝硬化患者的内毒素和脂多糖结合蛋白水平及其与预后的关系

背景脂多糖结合蛋白(LBP)是介导脂多糖(LPS)活化单核/巨噬细胞的关键因子。尽管内毒素在慢性肝病和肝硬化中具有重要作用,但其结合蛋白在肝硬化中的意义尚不清楚。目的了解肝硬化患者的内毒素和LBP水平,并探讨其与预后的关系。方法分别以基质显色法鲎试验和酶联免疫吸附测定(ELISA)检测肝硬化患者的血浆内毒素和LBP水平;伴腹水患者同时测定腹水内毒素和LBP水平,并进行2个月的短期随访,记录存活情况。结果肝硬化患者的血浆内毒素和LBP水平均显著高于健康对照者(P<0.05),其中伴腹水患者的血浆内毒素水平显著高于无腹水患者(P<0.05)。Child鄄PughC级肝硬化伴腹水患者的腹水内毒素水平显著高于B级患者(P<0.05),而B级患者的血浆LBP水平显著高于C级患者(P<0.05)。短期随访显示肝硬化伴腹水死亡患者的腹水内毒素水平显著高于存活者(P<0.05)。结论肝硬化患者的血浆内毒素和LBP水平均升高,LBP水平升高可能是对肝硬化肠源性内毒素血症的一种持续的慢性炎症应答。腹水内毒素水平可以作为肝硬化伴腹水患者短期生存的一个预测指标。     

肝硬化患者小肠细菌过度生长与内毒素血症

目的　研究肝硬化患者小肠细菌过度生长与血浆内毒素、白细胞介素 (IL) 2、IL 6及肿瘤坏死因子 (TNF) α水平的关系。方法　 71例肝硬化患者行葡萄糖 氢呼气试验 (GHBT)检测小肠细菌过度生长情况 ,鲎实验检测血浆内毒素水平及ELISA法检测血浆IL 2、IL 6及TNF α水平 ;分析血浆内毒素与血浆IL 2、IL 6及TNF α水平之间的关系。结果　 71例肝硬化患者中 ,GHBT阳性者为 1 8例(2 5 3 % )。肝硬化伴与不伴小肠细菌过度生长者血浆内毒素分别为 (0 71 5± 0 2 2 9)Eu/L、(0 379±0 2 2 3)Eu/L(P <0 0 0 1 ) ;IL 2分别为 (1 9 1 5± 4 60 )ng/L、(9 41± 6 69)ng/L ;IL 6分别为 (93 2 9± 2 7 37)ng/L、(53 2 2± 2 8 31 )ng/L ;TNF α分别为 (42 1 8± 1 6 91 )ng/L、(2 7 72± 1 7 0 6)ng/L(P值均 <0 0 1 )。肝硬化患者血浆内毒素与IL 2、IL 6及TNF α存在直线正相关 ,相关系数分别为 0 894、0 857、0 845(P值均 <0 0 0 1 )。结论　肝硬化伴小肠细菌过度生长患者血浆内毒素、IL 2、IL 6、TNF α水平均增高 ,提示肝硬化小肠细菌过度生长是导致肝硬化患者出现内毒素血症的原因之一。肝硬化患者血浆内毒素水平升高与血浆IL 2、IL 6、TNF α水平升高相关 ,提示肝硬化患者内毒素血症可刺激机体产生多     

银屑病与免疫分子关系的研究进展

银屑病的组织学特点是明显的炎性细胞浸润和角质细胞增生,浸润的细胞主要是记忆型细胞、中性粒细胞、内衬巨噬细胞及增多的树突状细胞。有证据表明,涉及的免疫机制主要是T淋巴细胞在靶部位的浸润进而产生IFN-γ等介质,诱导表皮细胞增生及活化角质细胞。现将银屑病与免疫分子关系的研究进展综述如下。     

库普弗细胞SR表达变化与内毒素肝损伤的关系

目的 观察内毒素肝损伤过程中库普弗细胞（KC）清道夫受体（SR）表达的动态变化,进而探讨内毒素肝损伤的机理。方法 经尾静脉内注射不同剂量（1mg/kg、10mg/kg）大肠杆菌内毒素（LPS）,复制内毒素肝损伤模型,采用免疫组织化学方法观察小鼠肝脏SR表达变化;酶联免疫吸附法（ELISA）测定肝组织TNFFα、IL－6的水平,光镜观察肝组织学变化。结果 （1）内毒素肝损伤过程中,KC表面SR表达呈进行笥下调,且与内毒素呈明显的量效关系。（2）SR表达的平均光密度值（A值）与肝组织TNFα、IL－6及血清ALT、TBil呈显著的负相关。结论 内毒素肝损伤过程中,随着SR表达下调,KC对内毒素的清除作用下降,内毒素对KC的激活作用则相应增强。KC SR表达变化与肝损伤密切相关。     

内毒素与胰腺损伤

内毒素(endotoxin )主要见于革兰阴性细菌,是细胞壁中脂多糖的组成成分.临床研究表明,急性胰腺炎,尤其是重症急性胰腺炎状态下存在着内毒素血症,并认为与急性胰腺炎的发生、发展及并发多脏器衰竭密切相关,其作用机制尚未阐明.我们着重概述内毒素导致胰腺损伤的实验和临床研究进展.     

酒精性肝病的内毒素损伤机制

据统计，酗酒者中，只有30％进展到肝硬化，提示在酒精诱导的肝损伤中还需要其它辅助因素，肠道的内毒素就是其中一种重要的辅因子。许多动物实验及临床研究均证实，酒精性肝损伤时常伴发内毒素血症，肠源性内毒素血症在酒精性肝病（ALD）的发生，发展及预后转归中起着重要作用。     

内毒素结合蛋白和慢性肝病

内毒素血症与肝脏疾病关系密切。近年的研究发现一些血浆蛋白能以特异或非特异的方式结合内毒素或中和内毒素，改变内毒素的生物学活性。目前研究较为广泛的是脂多糖结合蛋白(1ipopolysaccharide-binding protein，LBP)，可溶性CD14(soluble CD14，sCD14)，杀菌／渗透性增加蛋白(bactericidal／permeability increasing protein，BPI)，高密度脂蛋白等。本旨在探讨这些内毒素结合蛋白对内毒素作用的影响及其在慢性肝病中的意义。     

慢性肝病患者血清肿瘤坏死因子—α与白细胞介素—8水平关系的研究

用RIA法测94例慢性肝炎、肝硬化患者血清肿瘤坏死因子α(TNF-α)含量,同时用ELISA法测定其血清白细胞介素—8(IL—8)水平。结果表明慢性活动性肝炎和肝硬化患者血清中TNF-α明显高于对照组(P<0.01,P<0.05),且与其血清胆红素(BIL)和ALT呈正相关(P<0.05)。IL—8的阳性检出率及水平明显高于对照组(P<0.05～0.01),与其血清总胆红素(TB)亦呈正相关(P<0.05)。另外,患者血清TNF-α和IL—8定量明显相关(P<0.05)。提示TNF-α和IL—8参与了慢性肝脏炎症损害过程,并能反映病情活动程度,且TNF-α可能诱导IL—8的产生。     

慢性肝病血管新生研究

慢性肝病血管新生是导致肝硬化和肝硬化门静脉高压的重要因素。血管新生增加肝内血管阻力和减少有效肝细胞灌注,导致慢性肝病进展为肝硬化;另一方面血管新生调控门-体侧支循环的形成,增加内脏血流量,导致肝硬化门静脉高压及其并发症的发生。近年来针对血管新生与肝硬化形成的关系及门脉高压血管新生的机制行了大量研究,现综述如下。     

Relevance of endotoxin receptor CD14 and TLR4 gene variants in chronic liver disease

Objective. The lipopolysaccharide (LPS)-triggered release of inflammatory cytokines from Kupffer cells is mediated via the CD14/TLR4 receptor complex. This inflammatory pathway can be influenced by alterations in genes encoding for LPS receptor components. Thus, a -260 C>T transition in the CD14 promoter is thought to result in enhanced CD14 expression thereby increasing the LPS responsiveness in chronic liver diseases, whereas a D299G exchange in the TLR4 gene has the opposite effect. Our objective was to analyze these two variations. Material and methods. The study comprised 1712 patients with chronic liver diseases of different etiologies and 385 healthy controls. Genotyping was carried out by melting curve analysis with fluorescence resonance energy transfer (FRET) probes in the LightCycler. Results. Genotype frequencies of CD14 -260C>T and TLR4 D299G did not significantly differ between patients and controls (CD14 TT 21.6% versus 21.8%; TLR4 DG or GG 9.7% versus 10.4%). We found no significant correlation of these alterations with disease course either in the groups of patients with alcoholic liver disease or hepatitis C virus (HCV) infection or among patients requiring liver transplantation. A significantly higher frequency of the CD14 -260TT genotype was observed (36.6% versus 21.8% in healthy controls, p=0.036) only in a small subgroup of patients (n=41) with mild cryptogenic chronic liver disease. Conclusions. Variants within these LPS receptor genes were equally distributed among patients with chronic liver diseases of different etiologies and obviously do not confer an increased risk for the severity of these chronic liver processes.     

内毒素与脂肪肝的关系研究进展

脂肪肝时常伴有肠源性内毒素血症,内毒素不仅对肝细胞有直接的损伤作用,而且可通过激活库普弗细胞(KC)释放一系列生物活性物质,以及可能促进肝脏自然杀伤T细胞减少,导致促炎和抗炎免疫反应失衡,引起肝脏损害,从而加重内毒素的作用.     

Nutrition and chronic liver disease

Nutritional abnormalities almost uniformly accompany the metabolic disturbances of severe chronic liver disease and may adversely affect patient well-being and survival, especially surrounding liver transplantation surgery. The exact metabolic alterations responsible for malnutrition and its consequences in these patients have been debated and are a focus of this review. Disturbances in energy production and utilization, as well as macro- and micronutrient metabolism have been appreciated but are not always easily identified or quantifiable. Interestingly, the manifestations of poor nutritional status can vary substantially between patients, even in those having the same etiology and severity of illness. Proper assessment of patients with liver disease for malnutrition carries its own challenges, but some of the more easily applied techniques, such as anthropometry, can be comparable in accuracy to more sophisticated measuring tools. Gaining an appreciation and understanding of how nutritional disturbances develop and can contribute to morbidity and mortality will help combat inappropriate nutritional losses in this specialized group of patients. In many instances, simple adjustments in diet can offset losses and stabilize or improve the patient's nutritional status.     

内毒素及其结合因子与酒精性肝病的相关性

目的　探讨内毒素及其结合因子与酒精性肝病 (ALD)发生、发展的关系。方法　选取 3 0例ALD患者和 3 0例健康体检者分别作为ALD组与对照组 ,ALD组按临床体征、肝功能和(或 )肝脏B超、病理分为轻、中、重型。均分别检测丙氨酸氨基转移酶 (ALT)、天冬氨酸氨基转移酶(AST)、总胆红素 (TBIL)、内毒素、脂多糖结合蛋白 (LBP)、sCD14、载脂蛋白A1 、A2 、B (ApoA1、ApoA2、ApoB)等指标。 结果　ALD组的ALT、AST、TBIL、内毒素、LBP、sCD14与对照组比较均显著升高 (P <0 .0 5 ) ,且轻、中型ALD患者内毒素、sCD14增加非常显著 (P <0 .0 1) ;轻、中型ALD患者ApoA1、ApoA2显著升高 (P <0 .0 5 ) ,重型患者则减少 ;ApoB在各组患者中变化不明显。内毒素与LBP和sCD14显著相关 (P <0 .0 5 )。结论　内毒素及其结合因子在不同程度的酒精性肝病中的表达有差异 ,提示它们在酒精性肝病的发生、发展中起一定的作用     

Papaverine-induced chronic liver disease

The case history of a women with jaundice and laboratory evidence of chronic active hepatitis and cirrhosis is reported. The patient had taken papaverine for 6 yr for cerebral arterial disease. Jaundice improved after the drug was discontinued but reappeared when papaverine therapy was reintroduced. Antinuclear antibody and smooth muscle antibody were present. Clinical manifestations disappeared and laboratory results again returned to normal upon withdrawal of papaverine. This case suggests that papaverine should be added to the list of drugs known to produce chronic active hepatitis and cirrhosis.     

Complications of chronic liver disease

Children with chronic liver disease (CLD) need a head to toe approach and an early suspicion of multi organ involvement. Nutritional assessment and management is the cornerstone of management. Consider immune dysfunction in everyday treatment decisions. Consider early heart-lung-brain involvement in transplant evaluation.