膝关节液中透明质酸和Ⅱ型胶原羧基端端肽含量与滑膜炎关系的实验研究

目的探讨关节液中透明质酸(HA)和Ⅱ型胶原羧基端端肽(CTX-Ⅱ)含量与骨关节炎(OA)滑膜炎的关系。方法采用酶联免疫吸附试验对膝OA67例患者(OA组)、膝关节其他疾病77例患者(非OA组)的关节液中HA和CTX-Ⅱ含量进行检测,并在关节镜下利用Ayral滑膜炎评分法对滑膜炎程度进行评价。结果OA组关节液中HA含量明显低于非OA组(P<0.05);OA组关节液中CTX-Ⅱ含量高于非OA组(P<0.05);OA组关节液中HA含量与滑膜炎程度呈负相关,CTX-Ⅱ含量与滑膜炎程度呈正相关(P<0.05)。结论关节液中HA和CTX-Ⅱ含量是可反映OA滑膜炎的标志物。     

转化生长因子-β_1对兔膝骨关节炎软骨细胞凋亡的抑制作用

<正>骨关节炎(osteoarthritis,OA)主要的病理改变是关节软骨的退行性变化,这是因为在OA时关节液中大量炎症因子产生,如白细胞介素(IL)-1、IL-6、一氧化氮(NO)等。这些炎症     

IL-23p19 mRNA在RA患者滑膜组织及滑膜细胞中的表达

目的:探讨类风湿性关节炎(RA)与骨性关节炎(OA)患者滑膜组织及体外培养滑膜成纤维细胞(SF)中白细胞介素(IL)-23p19mRNA分泌来源及对RA诊断的意义。方法:收集行滑膜切除术及关节置换术的6例RA患者及6例OA患者滑膜组织,酶消化法对滑膜组织行SF体外培养,RT-PCR方法检测RA和OA滑膜组织、SF中IL-23p19mRNA表达水平,RA患者滑膜组织、SF中IL-1βmRNA的表达水平。结果:(1)6例RA患者和4例OA患者滑膜组织、SF或OASF中IL-23p19mRNA表达均为阳性,且RA患者滑膜组织中的表达高于OA患者,RASF中的表达量显著高于OASF中阳性标本的表达量(均P<0.05)。(2)6例RA患者滑膜组织中IL-1βmRNA表达均阳性,且与IL-23p19mRNA表达水平呈正相关(r=0.900,P<0.05),6例RASF中IL-1βmRNA表达均阳性,且与IL-23p19mRNA表达水平正相关(r=0.883,P<0.05)。结论:IL-23参与了RA的发病过程,并且可由RA患者中的SF分泌,IL-23可作为RA与OA鉴别诊断的指标之一,IL-1β很可能是IL-23在RA中发挥致病作用的途径之一。     

膝关节液透明质酸含量与滑膜炎程度的关系

目的探讨膝关节液透明质酸含量与滑膜炎程度之间的关系。方法酶联免疫吸附试验(ELISA)检测膝关节疾病(OA)患者102例共104膝的关节液透明质酸含量,并在关节镜下应用Ayral滑膜炎评分法和Outerbridge关节软骨损伤评分法评价膝滑膜炎和关节软骨损伤程度。采用t'检验、Spearman相关分析和多元线性回归分析进行统计分析。结果Ayral滑膜炎评分≥60分组的关节液透明质酸含量比Ayral滑膜炎评分<60分组高(P<0.001)。104膝关节液透明质酸含量与Ayral滑膜炎评分呈正相关(茁'A=0.497,P<0.001),与Outerbridge软骨损伤累计评分呈负相关(茁'o=-0.364,P<0.001),且Ayral滑膜炎评分的影响较大。关节液透明质酸含量与Ayral滑膜炎评分在Ayral滑膜炎评分≥60分组呈正相关(r=0.306,P<0.05),在Ayral滑膜炎评分<60分组无相关性(r=-0.144,P>0.05)。与非OA组相比,OA组的关节液透明质酸含量较低(P<0.05),而Ayral滑膜炎评分较高(P<0.01)。结论膝关节液透明质酸可作为生物标记物反映滑膜炎的程度,关节液透明质酸含量的增高提示滑膜炎较重。     

白细胞介素-37的生物属性及与类风湿关节炎的关系

<正>白细胞介素(IL)-37是2000年发现的IL-1家族的新成员,并在2001年根据其前体肽命名为IL家族的第七因子IL-1F。其功能为一个基本的先天炎症免疫抑制剂。目前,关于IL-37与自身免疫病类风湿关节炎(RA)之间关系的研究仍然处于空白。RA是一种以炎症反应造成的肉芽组织和纤维增生,使得关节腔内的血供严重受损的免疫系统疾病。严重的缺血使得局部出现坏死,以累及周围关节为主,其基本病理改变为滑膜炎。RA的滑膜组织中有大量的CD4+T细胞及其分泌的IL-2、干扰     

黄柏五味膏对兔膝骨性关节炎中滑膜炎的防治

目的通过对肿瘤坏死因子-α(TNF-α)和基质金属蛋白酶-3(MMP-3)的检验,讨论黄柏五味膏通过治疗滑膜炎症从而减轻骨性关节炎(OA)的症状的原理。方法试验选取健康日本大白兔40只随机分成4组,分别为:空白组、模型组、对照组、黄柏五味膏试验组。取兔右膝关节作为试验造模关节,使用鬼头康彦的造模方法造OA滑膜炎模型,造模成功7 d后使用黄柏五味膏外敷。8周后处死试验大白兔并取右膝关节滑液,用ELISA法检测关节液中TNF-α、MMP-3水平。结果黄柏五味膏实验组TNF-α及MMP-3水平均明显低于模型组,并具有统计学意义,而黄柏五味膏实验组TNF-α及MMP-3水平均与对照组无明显差别且无统计学意义。结论实验结果证明黄柏五味膏可降低骨性关节炎滑膜炎模型的TNF-α及MMP-3水平,对滑膜炎的防治及保护软骨有显著作用,从而减轻OA症状。     

性病患者58例血清IL-2、IL-6和IL-8水平的检测及其临床意义

目的　探讨血清白细胞介素 - 2 (IL- 2 )、白细胞介素 - 6 (IL- 6 ) ,白细胞介素 - 8(IL- 8)在性病患者血清中水平及临床意义。方法　应用双抗体夹心 Eli SA法检测了 5 8例性病患者血清中 IL- 2、IL- 6和 IL- 8水平。结果　 5 8例性病患者血清中 ,IL - 2、IL - 6、IL - 8水平分别为 (6 .4± 3.2 ) ng/ ml、(0 .15± 0 .0 6 ) ng/ ml、(0 .34± 0 .13) ng/ m l、而 IL - 8则显著高于正常人组 (P<0 .0 1) ,其中 IL- 2、IL- 6则明显低于正常人组 (P<0 .0 1)。结论　性病患者的发生与发展与IL - 2、IL - 6降低和 IL - 8升高密切相关 ,检测 IL - 2、IL - 6和 IL - 8血清水平有助于性病的判断和治疗的选择     

类风湿关节炎患者血清白细胞介素-32细胞间黏附分子-1白细胞介素-10的检测及意义

目的通过对类风湿关节炎(RA)患者血清白细胞介素(IL)-32、细胞间黏附分子-1(ICAM-1)、IL-10的检测,探讨IL-32、ICAM-1、IL-10在RA发病、病程发展中的意义及临床相关性。方法采用酶联免疫吸附试验(ELISA),检测115例RA、31例骨关节炎(OA)、76名对照组IL-32、ICAM-1、IL-10的水平,并与抗环瓜氨酸肽(CCP)抗体、类风湿因子(RF)、超敏C反应蛋白(hs-CRP)、红细胞沉降率(ESR)等指标进行相关性分析。结果3组比较,RA组、OA组血清IL-32、ICAM-1、IL-10浓度高于对照组,差异有统计学意义(P<0.05);RA重度活动期组IL-32、ICAM-1浓度显著高于缓解期组(P<0.05);RA组血清IL-32、ICAM-1水平与抗CCP抗体、RF、ESR、hs-CRP、28个关节疾病活动指数(DAS28)、关节肿胀数和关节压痛数呈正相关(P<0.01),IL-10与ESR、hs-CRP呈正相关(P<0.05或P<0.01)。结论 IL-32、ICAM-1、IL-10参与了RA形成,并与疾病活动程度关系密切。研究IL-32、ICAM-1、IL-10在RA病理生理过程中的生物学效应,有助于RA发病机制的研究,为临床治疗提供依据。     

蛛网膜下腔出血患者白细胞介素-6变化特征

目的　了解蛛网膜下腔出血 (SAH )患者血清及脑脊液 (CSF)中白细胞介素 - 6 (IL - 6 )的动态变化特征 ,并研究 IL - 6与脑血液循环动力学、血糖等之间的关系。方法　选用双抗体夹心酶联免疫吸附试验 (EL ISA)检测 SAH组患者血清及 CSF中的 IL - 6浓度。将 IL - 6水平与临床各指标间关系进行了相关分析。结果　 SA H组血清 IL- 6水平在急性期明显高于对照组 ,而 CSF中 IL- 6水平明显高于其血清中以及对照组 CSF中水平 ,且与血流动力学指标等具有相关性。结论　 IL- 6在 SAH的发病机制及病理生理过程中起重要作用 ,早期检测血清中IL- 6可以为预测早期预后以及指导治疗提供依据     

腹腔注射γIL-2对原发性肝癌腹水及血清IL-6 IL-12 NO内毒素的作用

目的 :探讨 γIL- 2对原发性肝癌腹水及血清 IL- 6,IL- 12 ,一氧化氮 (NO)和内毒素的影响。方法 :腹膜腔注射 γIL- 2后 ,检测原发性肝癌患者腹水及血清的 IL- 6,IL- 12 ,NO和血浆内毒素水平。结果 :γIL- 2可显著提高患者血清和腹水 IL - 6和 IL - 12浓度 ,降低腹水和血浆 NO水平 ,降低腹水内毒素浓度。结论 :腹腔注射γIL - 2对原发性肝癌可能有重要作用     

Intra-articular Injection of Urinary Bladder Matrix Reduces Osteoarthritis Development

Micronized porcine urinary bladder matrix (UBM) is an extracellular matrix biomaterial that has immunomodulatory and pro-regenerative properties. The objective of this study was to assess the ability of UBM to alter disease progression in a mouse model of post-traumatic osteoarthritis (OA). Ten-week-old wild-type C57BL/6 male mice underwent anterior cruciate ligament transection (ACLT) to induce OA. Two weeks after ACLT, UBM (50 mg/mL) or saline was injected into the mouse joint. At 4 and 8 weeks post-ACLT, cartilage integrity was assessed using OARSI scoring of histology, pain was evaluated, and joints were harvested for quantitative RT-PCR analysis of cartilage-specific and inflammatory gene expression. UBM-treated animals showed improved cartilage integrity at 4 and 8 weeks and reduced pain at 4 weeks compared to saline-injected mice. Animals injected with UBM expressed higher levels of genes encoding structural cartilage proteins, such as collagen2α1 and aggrecan, as well as anti-inflammatory cytokines, including interleukins 10 and 4. UBM decreased cartilage degeneration in the murine ACLT model of OA, which may be due to reduced inflammation in the joint and maintenance of high expression levels of proteoglycans.     

骨关节炎软骨组织退变分子机制研究进展

骨性关节炎（OA）是一种非常普遍的疾病,可分为原发性和继发性。继发性OA有明确的致病原因。如创伤、炎性关节病、先天性或发育性骨关节病、代谢性或内分泌性疾病等;原发性OA病因及发病机制尚不十分明确,可能与年龄增长、过度使用、损伤、肥胖、遗传等多种因素密切相关。然而,OA分子作用机制是复杂的,目前尚没有有效的治疗。OA的启动和发展是一个复杂的过程,在分子水平上,可能包括许多细胞类型。信号通路和细胞外基质的变化。本文的研究重点在于OA产生的分子机制与最新研究结果的相关性。     

促炎症因子与骨性关节炎关系的研究进展

骨性关节炎（osteoarthritis,OA）是我国老年人关节疼痛和功能障碍的主要原因,发病率逐年上升。除关节周缘骨赘增生和关节软骨退变外,炎症作为OA重要的病理改变之一,得到越来越广泛的关注。促炎症因子是炎症反应重要的媒介,OA中促炎症因子水平升高,导致全身和局部的炎症反应、加速包括关节软骨在内的多种组织结构破坏,促进OA进展的理念已被广大学者接受。此外,炎症严重程度和OA的临床表现密切相关。因此,深入了解各种促炎症因子在OA发病中的作用具有重要的临床意义。本文从促炎症因子与OA的关系及分子机制角度入手,对该领域的研究进展作一综述,为OA的临床诊治提供新的视角。     

MMP-7在骨关节炎中的表达

目的：检测骨关节炎（OA）患者退变关节软骨中基质金属蛋白酶－7（MMP－7）的表达，以便进一步了解骨关节炎的发病机制。方法：运用免疫组织化学抗生物蛋白－生物素－过氧化物酶复合体法，通过抗MMP－7的单克隆抗体对40例骨关节炎患者和15例正常者关节软骨标本进行染色。结果：骨关节炎软骨中的MMP－7的表达比正常者增多，其差异有极显著意义。结论：MMP－7与骨关节炎关节骨退变有关。姑骨关节炎关节骨退变的病理过程中发挥关键作用。     

脑源性白介素的研究进展

传统观点认为白介素是由免疫细胞产生的 ,然而 ,许多研究资料表明 ,神经元和神经胶质细胞也能够产生和分泌白介素 ,即脑源性白介素。脑源性白介素可与中枢神经系统多种神经递质相互作用 ,影响动物的行为、学习记忆 ,并与早老性痴呆、抑郁症等疾病相关。深入研究脑源性白介素对理解许多疾病的病理生理进程有积极意义     

Interleukins in atherosclerosis: molecular pathways and therapeutic potential

Interleukins are considered to be key players in the chronic vascular inflammatory response that is typical of atherosclerosis. Thus, the expression of proinflammatory interleukins and their receptors has been demonstrated in atheromatous tissue, and the serum levels of several of these cytokines have been found to be positively correlated with (coronary) arterial disease and its sequelae. In vitro studies have confirmed the involvement of various interleukins in pro-atherogenic processes, such as the up-regulation of adhesion molecules on endothelial cells, the activation of macrophages, and smooth muscle cell proliferation. Furthermore, studies in mice deficient or transgenic for specific interleukins have demonstrated that, whereas some interleukins are indeed intrinsically pro-atherogenic, others may have anti-atherogenic qualities. As the roles of individual interleukins in atherosclerosis are being uncovered, novel anti-atherogenic therapies, aimed at the modulation of interleukin function, are being explored. Several approaches have produced promising results in this respect, including the transfer of anti-inflammatory interleukins and the administration of decoys and antibodies directed against proinflammatory interleukins. The chronic nature of the disease and the generally pleiotropic effects of interleukins, however, will demand high specificity of action and/or effective targeting to prevent the emergence of adverse side effects with such treatments. This may prove to be the real challenge for the development of interleukin-based anti-atherosclerotic therapies, once the mediators and their targets have been delineated.     

Leptin – A Link between Obesity and Osteoarthritis. Applications for Prevention and Treatment

Osteoarthritis (OA) is the most common cause of musculoskeletal disability and pain in the world. The current drug treatment for OA is symptom relieving, and there is an urgent need for treatments that could retard, prevent or repair cartilage destruction in OA. Obesity is a major risk factor for OA. Traditionally, it has been thought to contribute to the development of OA by increasing the load on weight‐bearing joints. However, this appears to be an over‐simplification, because obesity is also linked to OA in the hand and finger joints. Recent studies have shown that adipocytokine leptin is a possible link between obesity and OA: Leptin levels in synovial fluid are increased in obese patients, leptin receptor (Ob‐R) is expressed in cartilage, and leptin induces the production of matrix metalloproteinases (MMPs), pro‐inflammatory mediators and nitric oxide (NO) in chondrocytes. Furthermore, according to the very recent findings, not only leptin levels in the joint but also leptin sensitivity in the cartilage are enhanced in obese OA patients. The findings supporting leptin as a causative link between obesity and OA offer leptin as a potential target to the development of disease‐modifying drugs for osteoarthritis (DMOAD), especially for obese patients.     

Okadaic Acid Depuration from the Cockle Cerastoderma edule

The cockle Cerastoderma edule is a commercially important species in many European Countries. It can accumulate okadaic acid (OA) and other toxins in its group, which makes it unsuitable for human consumption, producing harvesting bans to avoid intoxications. The duration of those bans depends in part on the depuration kinetics of the toxin in this species. In this work, this kinetics was studied by means of fitting different models to depuration data experimentally obtained, using naturally contaminated cockles. Cockles depurated OA faster than most other bivalve species studied. Models that include Michaelis-Menten kinetics describe the depuration better than those using a first order exponential decrease to describe the first (or the only) compartment. One-compartment models were not able to describe the final part of the depuration curve, in which OA was depurated very slowly. Therefore, two-compartment models were needed. Esters were depurated at a much faster rate than the free form of the toxin; however, no significant esterification was detected during the process. The slow depuration rate suggests that other bivalve species could be used as sentinels to monitor cockle populations, but caution should be taken when toxin concentrations are very high.     

Study of possible combined toxic effects of azaspiracid-1 and okadaic acid in mice via the oral route

Toxins from the okadaic acid (OA) and azaspiracid (AZA) group cause considerable negative health effects in consumers when present in shellfish above certain levels. The main symptoms, dominated by diarrhoea, are caused by damage to the gastrointestinal (GI) tract. Even though OA and AZAs exert toxicity via different mechanisms, it is important to find out whether they may enhance the health effects if present together since they act on the same organs and are regulated individually. In this study, the main issue was the possibility of enhanced lethality in mice upon combined oral exposure to OA and AZA1. In addition, pathological effects in several organs and effects on absorption from the GI tract were studied. Although the number of mice was small due to low availability of AZA1, the results indicate no additive or synergistic effect on lethality when AZA1 and OA were given together. Similar lack of increased toxicity was observed concerning pathological effects that were restricted to the GI-tract. OA and AZA1 were absorbed from the GI-tract to a very low degree, and when given together, uptake was reduced. Taken together, these results indicate that the present practice of regulating toxins from the OA and AZA group individually does not present an unwanted increased risk for consumers of shellfish.     

Relative toxicity of dinophysistoxin-2 (DTX-2) compared with okadaic acid, based on acute intraperitoneal toxicity in mice.

When substituting the mouse bioassay for lipophilic marine algal toxins in shellfish with analytical methods, science based factors of relative toxicity for all analogues that contribute to health risk to consumers are necessary. The aim of this paper is to establish the relative intraperitoneal toxicity of dinophysistoxin-2 (DTX-2) compared with okadaic acid (OA). The study was performed as an open, randomised parallel group trial with a four level response surface design within each of the two parallels. In accordance with the response surface design model, the LD50 for DTX-2 and OA was 338 and 206 microg/kg, respectively. By use of common regression analysis, the LD50 of DTX-2 and OA were estimated to 352 microg/kg and 204 microg/kg, respectively. The deviations between the LD50 estimates by the two methods was 4% for DTX-2 and less than 1% for OA. Taken together, these results indicate that the relative toxicity of DTX-2 is about 0.6, compared to OA. Results from the PP2A assay correspond very well with the results obtained by the mouse bioassay. The IC50 concentrations for DTX-2 and OA were 5.94 and 2.81 ng/mL, respectively. This indicates that OA is about twice as toxic as DTX-2. Since inhibition of PP2A is acknowledged as the main mechanism of toxicity of the OA group toxins, this supports the establishment of a relative toxicity factor of DTX-2 of 0.6 compared with OA.