胶原诱导性关节炎小鼠存在血管内皮功能失调——类风湿关节炎加速动脉粥样硬化的新证据

目的类风湿关节炎(RA)患者易患动脉粥样硬化(AS),而RA是否会造成内皮功能障碍,并通过该途径触发或者加速AS是我们的研究重点。方法观察胶原诱导性关节炎(CIA)小鼠及同期对照小鼠的主动脉对于乙酰胆碱及硝普纳诱导的血管舒张率并进行对比,及CIA与对照小鼠血管组织iNOS及eNOS表达水平的检测。结果对照小鼠的主动脉组织中,对于乙酰胆碱的诱导,血管舒张率为88.70±22.90%,CIA显著下降为53.90±18.40%(p<0.01)。对于硝普纳的诱导则未见差异。CIA小鼠血管组织中eNOS表达下调,iNOS表达升高。结论 CIA小鼠存在内皮细胞功能障碍且与关节炎严重程度呈正相关。     

Accelerated atherosclerosis in pre-menopausal female patients with rheumatoid arthritis

Increased mortality due to cardiovascular disease in rheumatoid arthritis (RA) patients was reported. Using B-mode ultrasonography we compared intima-media thickness (IMT) and plaque occurrence (indicators of asymptomatic atherosclerosis) in the carotid arteries in 70 pre-menopausal, female RA patients and 40 controls. Correlations with different risk factors were evaluated. The IMT values were higher in RA patients (0.59 mm vs. 0.47 mm, P < 0.0001) and they had more plaques (P = 0.023). In RA patients higher levels of sensitive CRP (P < 0.0001), ICAM (P < 0.0001), VCAM (P < 0.0001), IL-2 (P < 0.001), IL-6 (P = 0.009) and TNF-alfa (P < 0.01) were found. A correlation between IMT and triglycerides (P = 0.018) and a negative correlation between IMT and HDL cholesterol (P = 0.037) were found. With multiple regression analysis the association between IMT and sensitive CRP (P = 0.027) and presence of plaques and apolipoprotein B (P = 0.028) was established. The results indicate that even pre-menopausal, female RA patients had accelerated atherosclerosis. Chronic systemic inflammation may play an important role in atherogenesis.     

Atherosclerosis and inflammation: insights from rheumatoid arthritis

Cardiovascular disease is a major health care problem and the most common cause of death among individuals from developed nations. Our understanding of atherosclerosis has evolved from a passive process resulting in narrowing of the lumen and consequent myocardial ischemia to a dynamic process that involves inflammation. The study of atherosclerosis in patients with chronic inflammation, such as rheumatoid arthritis (RA), will provide insights into the relationship between inflammation and atherosclerosis. We review the relationship between atherosclerosis and inflammation within the context of RA, providing evidence that patients with RA have increased cardiovascular morbidity and mortality and accelerated coronary and extra-coronary atherosclerosis. In addition, traditional and novel cardiovascular risk factors are discussed. Finally, actions that a rheumatologist can take to better control this cardiovascular morbidity are suggested. These can be summarized as follows: (1) careful assessment and treatment of cardiovascular risk, (2) better control of inflammation, and (3) individual risk–benefit evaluation of need for cyclo-oxygenase-2 inhibitors, nonsteroidal anti-inflammatory drugs, and high doses of corticosteroids. Presented as Medicine Grand Rounds at the University of Alberta. This review was supported by grants (HL04012 and HL67964) from the National Institutes of Health.     

炎症消散的缺失诱发As斑块形成的作用机制及中药复方干预As炎症新思路的探索

动脉粥样硬化（As）是心脑血管疾病发病和死亡的主要病理基础之一。抗炎是防治As的一条有效途径,一些新型的抗炎药物已经进入了临床研究阶段。近年来的研究发现,炎症消散的缺失也是As斑块形成和破裂的重要因素。本文基于抗炎治疗在As防治中的研究进展,从炎症消散的角度出发,系统总结了炎症消散各方面的缺失对As斑块形成的影响。并深入探讨了胞葬作用在As早期和As斑块成熟期的变化及其所呈现出不同结果的原因。此外,本文结合As炎症消散缺失的作用机制,思考并探讨中医药干预As炎症消散可能的作用靶点,为寻求针对抗炎和促炎症消散双方面调节的抗As药物提供科学依据和理论参考。     

动脉粥样硬化大鼠Chemerin与炎症的相关性

目的 探讨动脉粥样硬化大鼠血浆Chemerin及主动脉Chemerin基因和Chemerin受体基因表达与炎症的相关性。方法 健康雄性Wistar大鼠82只,分为对照组、辛伐他汀治疗组及高脂组,喂养14周处死,行心脏采血、分离胸主动脉及腹主动脉备HE染色及RT-PCR,ELISA法检测三组大鼠血浆Chemerin、hs-CRP、IL-6、TNF-β水平,半定量RT-PCR技术检测三组大鼠主动脉Chemerin及Chemerin受体mRNA 水平。结果 高脂组大鼠动脉粥样硬化形成良好。三组大鼠间血浆Chemerin、hs-CRP、IL-6、TNF-β水平差异具有统计学意义,呈高脂组>辛伐他汀治疗组>对照组（P<0.05）;对照组、高脂组及辛伐他汀治疗组大鼠血浆Chemerin均与hs-CRP呈正相关,r值分别为0.664、0.804和0.709（P<0.05）;三组大鼠间主动脉Chemerin mRNA及Chemerin受体mRNA表达水平差异具有统计学意义,呈高脂组>辛伐他汀治疗组>对照组（P<0.05）;高脂组、辛伐他汀治疗组Chemerin mRNA及Chemerin受体mRNA表达水平与hs-CRP、IL-6、TNF-β呈正相关（P<0.05）。结论 动脉粥样硬化大鼠血浆Chemerin水平、主动脉Chemerin及Chemerin受体mRNA表达水平与炎症密切相关,这提示Chemerin-Chemerin受体通路在联系炎症与动脉粥样硬化之间发挥重要的作用。     

Lipoprotein(a) and Lipids in Relation to Inflammation in Rheumatoid Arthritis

The aim of this study is to evaluate whether lipoprotein(a) (Lp(a)) acts as the acute phase reactant and whether changes of lipids are related to inflammation in rheumatoid arthritis (RA). Lp(a) and lipids were measured after an overnight fast, before and after 14 days use of antiinflammatory agents and correlated with laboratory findings in 21 untreated RA patients and 19 healthy controls. Nine (42.3%) of 21 RA patients and 6 (31.6%) of 19 controls had high Lp(a) levels (> 30 mg/dl) and the Lp(a) level was higher in RA patients compared with controls (27.1 ± 5.3 vs 19.0 ± 4.2 mg/dl) without significant difference (p > 0.05). There was no significant correlation between ESR and Lp(a) and lipids in RA patients except for HDL cholesterol (r=–0.563, p = 0.008). After antiinflammatory agent use for 14 days, change in ESR (ESRsample1–ESRsample2) was significantly and negatively correlated to changes in total and HDL cholesterols in RA patients. In conclusion, although Lp(a) tended to be higher in RA, we could not find a distinct acute phase pattern of Lp(a). But changes in total and HDL cholesterols were negatively correlated with inflammation in RA. Our data support the phenomenon that dyslipoproteinemia observed in RA is associated with inflammation. Received: 6 August 1999 / Accepted: 25 January 2000     

Oral Candida Colonization as a Risk Factor for Chronic Inflammation and Atherosclerosis in Hemodialysis Patients

The purpose of this study was to determine the prevalence of oral Candida spp. in HD patients and to investigate its relation with systemic inflammation and atherosclerosis. Microbiological samples were taken from buccal mucosa, palate, and dental prosthesis with a cotton swab. High‐sensitivity CRP (hsCRP) and IL‐6 were measured as inflammation markers. A total of 69 patients (58% male and median age 62 years) were enrolled in this study; 53.6% of total patients had oral Candida colonization. HsCRP and IL‐6 levels were found to be significantly higher in the oral Candida colonization positive group than in the Candida colonization negative group (P = 0.002 and P = 0.01, respectively). HDL levels were significantly lower in the Candida colonization positive group (P = 0.03). Peripheral artery disease (P = 0.05) and oral Candida colonization (P = 0.002) were significantly associated with inflammation. In addition to conventional risk factors such as age (P = 0.03), diabetes (P = 0.001), and peripheral artery disease (P = 0.002), oral Candida colonization is associated with coronary artery disease (P = 0.04). Oral Candida colonization might be associated with chronic inflammation and development of atherosclerosis in HD patients.     

Sclerostin as an innovative insight towards understanding Rheumatoid Arthritis

BackgroundRheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation leading to cartilage and local bone erosion. Sclerostin is a protein that in humans has been identified as an inhibitor of the pathway and leads to decreased bone formation.Aim of the workThis study aimed to investigate the level of serum sclerostin in RA patients, its association with inflammatory profile and its relation to disease activity and severity.Patients and methodsThirty-one Egyptian RA patients (28 females, 3 men) participated in this study. Their median age was 40 years. Disease activity score was assessed by the disease activity score (DAS28) and the functional status by the modified health assessment questionnaire (MHAQ). Ten matched controls were also included. Radiological severity was assessed according to the Larsen score. Serum sclerostin was measured.ResultsMedian serum sclerostin in RA patients was 2000 ng/dl (800–3300 ng/dl) which was significantly higher than in controls [210 ng/dl (150–2859)] (Z = −4.47, p < 0.001). Sclerostin significantly negatively correlated with C-reactive protein and DAS28 (p = 0.014 and p = 0.02 respectively) and positively correlated with the Larsen score and total joint count (p = 0.03 and p = 0.02 respectively). At serum level 267 ng/dl sclerostin has sensitivity of 96.8% to diagnose RA and a positive predictive value of 96.6%.ConclusionSerum sclerostin was significantly higher in RA patients than controls and correlated with disease activity and severity which highly suggests that it may play a role in the pathogenesis of RA making it a valuable new marker of monitoring the disease progress and prognosis.     

炎症、动脉粥样硬化和心脑血管疾病

心脑血管疾病的病理基础是动脉粥样硬化,动脉粥样硬化被证实是细胞和分子的炎症反应。临床研究论证了炎症标记C 反应蛋白的增高预测心脑血管病发生的危险。C 反应蛋白已被美国心脏协会和疾病控制中心推荐为目前可信性最高的预测冠心病危险的临床检测指标,使极早期预测心脑血管疾病成为可能。至今发现的抗动脉炎症药物包括:阿司匹林、克皮格尔、他汀类降脂药和血管紧张素转换酶抑制剂。