Anti-inflammatory Effect of Polysaccharide from Embelia parviflora Wall.on Rheumatoid Arthritis in Rats

[Objectives]To investigate the anti-inflammatory effect of Embelia parviflora Wall.polysaccharide on rheumatoid arthritis(RA)in rats.[Methods]RA rat model was induced by type II collagen.After successful modeling,the rats were divided into model group,positive group,low,medium and high dose of E.parviflora Wall.polysaccharide groups,and normal control group.Body mass,toe volume and arthritis index were measured,and thymus index and spleen index were calculated.The levels of interleukin-1β,interleukin-6 and tumor necrosis factor-αin serum and synovial tissue of ankle joint were detected by ELISA.[Results]Compared with the normal control group,the pathological changes such as synovial hyperplasia and unclear layer were observed in the model group,the body mass was decreased(P<0.05),the toe volume,arthritis index,thymus and spleen index were increased(P<0.05),and the levels of IL-1β,IL-6 and TNF-αin serum and ankle synovial tissue were increased(P<0.05).Compared with the model group,the histopathological changes in synovium of ankle joint in the positive group and the medium and high dose groups of E.parviflora Wall.polysaccharide were significantly improved,and the body mass was increased(P<0.05).The toe volume,arthritis index,thymus index and spleen index were decreased(P<0.05).The levels of IL-Iβ,IL-6 and TNF-αin serum and synovial tissue of ankle joint were increased(P<0.05),while there was no significant difference between the low dose group of E.parviflora Wall.polysaccharide and the model group(P>0.05).[Conclusions]E.parviflora Wall.polysaccharide can reduce the body's inflammatory response and improve RA,which may be related to the inhibition of the activation of inflammatory cytokines IL-1β,IL-6 and TNF-α.

Design and evaluation of a novel transdermal patch containing diclofenac and teriflunomide for rheumatoid arthritis therapy

The aim of this study was to design a compound transdermal patch containing diclofenac(DA)and teriflunomide(TEF)for the treatment of rheumatoid arthritis(RA).The various organic amines salts of DA were prepared and their forming was confirmed using DSC and FTIR.The percutaneous permeation of organic amines salt of DA was investigated in vitro using a two-chamber diffusion cell with excised rabbit skin as transdermal barrier.The formulation of the patch was optimized in terms of the concentration of percutaneous permeation enhancer and the loading dose of drugs.The pharmacokinetic behavior of the optimal formulation was studies in rabbits and the anti-inflammatory and analgesic effects of the optimal patch were evaluated with the adjuvant arthritis model in rats and the pain model in mice,respectively.The result showed that skin penetration of diclofenactriethylamine(DA-TEtA)salt was better than other organic amine salts.Based on previous study of our laboratory,teriflunomide-triethylamine(TEF-TEtA)significantly enhanced the skin permeation of TEF.10%of azone(AZ)was the best enhancer for the two drugs.The optimal patch formulation was composed of 2%of TEF-TEtA,6%of DA-TEtA and 10%of AZ.The cumulative permeated amount of DA-TEtA in vitro was comparable with that of the commercial diclofenac-diethylamine(DA-DEtA)patch.The absolute bioavailability of TEFTEtA was 42%,which could achieve the therapeutic drug levels.In animal study,the optimized compound patch containing DA-TEtA and TEF-TEtA displayed significant antiinflammatory and analgesic effect,which indicated the potential of the compound patch.

The diagnostic significance of glucose-6-phosphate isomerase (G6PI) antigen and anti-G6PI antibody in rheumatoid arthritis patients

Objective: To investigate whether glucose-6-phosphate isomerase (G6PI) antigen and anti-G6PI antibodies could be applied for the clinical diagnostic markers of rheumatoid arthritis (RA) and its associations with RA activity states. Methods: The levels of G6PI antigens and anti-G6PI Abs in sera from 176 RA patients in different states, 35 non-RA patients and 100 healthy donors and in synovia fluids from 33 patients and 11 non-RA patients were measured by ELISA. Results: The sensitivity and specificity of G6PI antigens in the RA patients were 75.0% and 93.3%, respectively. The levels of serum G6PI antigens in 176 RA patients were significantly higher than non-RA patients and the health controls. Especially, there was a significant difference between the active phase and the inactive phase in G6PI antigens levels. The levels of G6PI antigens in synovia fluid were also significantly higher in RA groups than in non-RA patients. With the values of the anti-G6PI Abs in sera, there were no marked differences among RA, non-RA patients and health controls. Also, there was no significant difference between the active phase and the inactive phase in RA patients. However, there were no significant differences of G6PI and anti-G6PI between RA patients and health controls in synovial fluid. Conclusions: G6PI is highly correlated with the activity states of RA, and could be applied for a clinical biomarker with high sensitivity and specificity for the diagnosis of RA.

Study on Anti-Rheumatoid Arthritis Effect of Lignum Xanthocerais Sorbifoliae Based on Network Pharmacology

[Objectives]To explore the anti-rheumatoid arthritis effect of Lignum Xanthocerais Sorbifoliae by network pharmacology method.[Methods]The chemical constituents and action targets of Lignum Xanthocerais Sorbifoliae were collected by Traditional Chinese Medicine Systems Pharmacology(TCMSP).Target genes of rheumatoid arthritis(RA)were obtained from TTD database.ClusterProfiler was used for gene ontology(GO)enrichment,and Cytoscape 3.7.2 software was used for Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment and screening of active component-target core network.[Results]There were 24 intersecting targets between active components and diseases.The analysis of GO enrichment and KEGG pathway enrichment indicated that the therapeutic effect of Lignum Xanthocerais Sorbifoliae on rheumatoid arthritis might be related to AGE-RAGE signaling pathway,IL-17 signaling pathway,rheumatoid arthritis pathway,C-type signaling pathway and Toll-like receptor signaling pathway.13 drug active components[flavanes,dihydroflavonoids,stigmasterol,oleanolic acid,kaempferol,ellagic acid,Terchebulin B,Copaene,(Z)-β-Caryophyllene,Aromadendrene,β-Elemene,emodin]and 12 core targets(TNF,IL6,ALOX5,MAPK14,PPARA,AKR1B1,CCR5,PLA2G1B,ADAM17,MMP1,PTGS1,SYK)constituted a core network.[Conclusions]This study could provide a theoretical basis for the treatment of RA with Lignum Xanthocerais Sorbifoliae preparation.

May Traditional Chinese Medicine Reduce the Risk of Developing Rheumatoid Arthritis?An One-armed Prospective Study

Background:Rheumatoid arthritis(RA)is a worldwide public health problem.Intervention and prevention before the onset of rheumatic diseases is a new direction in current research.Objective:The aim of this study was to evaluate the potential and feasibility of traditional Chinese medicine(TCM)in the prevention of RA.Methods:This was a single-armed prospective clinical trial.All participants were recruited from a single center in Guangdong,China.Adults who were tested positive for anti-cyclic citrullinated peptide antibody(anti-CCP)and/or rheumatoid factor(RF),had no synovitis and never been treated with disease-modifying anti-rheumatic drugs(DMARDs),were enrolled to take the Huayu-Qiangshen-Tongbi(HQT)decoction orally twice daily,200 mL each time for 24 weeks.Primary outcome was the proportion of patients who met 2010 ACR(American College of Rheumatology)/EULAR(European League Against Rheumatism)classification criteria of RA during observation.Secondary outcomes included levels of anti-CCP,RF,erythrocyte sedimentation rate(ESR),C-reactive protein(CRP),assessment of signs and symptoms,and radiographic progression by magnetic resonance imaging(MRI).Results:19 individuals were enrolled in the study,4 of which withdrew because of the epidemic of COVID-19.During the observation period,3 individuals(20%)developed RA and they had longer morning stiffness(P=0.009)and more obvious synovial enhancement in MRI(P=0.041)at baseline when compared with those who did not develop RA.After 24 weeks of intervention,there were improvements in 28-swollen joint count(SJC28)(P=0.046),Visual Analog Scale(VAS)(P=0.019),Patient’s Global Assessment(PtGA)(P=0.019)and Physician’s Global Assessment(PGA)(P=0.031),but no statistical significance was observed in the levels of anti-CCP,RF,ESR,CRP,morning stiffness,28-tender joint count(TJC28),Health Assessment Questionnaire(HAQ)and magnetic resonance imaging(MRI)analysis(P>0.05).Conclusion:The HQT formula is safe and could improve joint symptoms and signs in these at-risk individuals,but it remains to be investigated in futher study to see if it might potentially reduce the risk of developing RA.Besides,for individuals at high risk to develop RA,morning stiffness and synovial enhancement in MRI might be predictive factors and warning signs.

电针对佐剂性关节炎大鼠膝关节滑膜VEGF/Vav2/Rac1信号通路的影响

目的观察电针对佐剂性关节炎(adjuvant arthritis,AA)大鼠膝关节滑膜组织内血管内皮生长因子(vascular endothelial growth factor,VEGF)、鸟嘌呤核苷酸交换因子2(vav guanine nucleotide exchange factor 2,Vav2)和Ras相关C3肉毒素底物1(Ras-related C3 botulinum toxin substrate 1,Rac1)表达的影响,探究电针干预类风湿关节炎(rheumatoid arthritis,RA)血管新生的可能机制。方法将40只SPF级SD雄性大鼠随机分成4组(空白组、模型组、西药组和电针组),每组10只。除空白组,其他3组采用尾根部皮下注射完全弗氏佐剂制成AA大鼠模型。造模后第2天开始干预,电针组进行电针干预,以左侧足三里与关元穴配穴,右侧足三里与同侧阿是穴配穴,每次20 min,每天干预1次,共干预21次;西药组给予甲氨蝶呤灌胃给药,每周1次,共干预3次。观察各组体质量、关节红肿等一般情况,每3天测量1次大鼠后双侧足跖容积。干预结束后,通过大鼠一般情况、体质量、足跖容积分析各组大鼠足跖肿胀程度,HE染色观察AA大鼠膝关节滑膜组织的病理形态学,免疫组织化学法检测膝关节滑膜组织内CD31表达变化,Western blot法检测大鼠膝关节滑膜组织VEGF、Vav2和Rac1蛋白表达量。结果与空白组相比,模型组大鼠第21天足跖容积均明显增大(P<0.01),膝关节滑膜组织出现显著性病理改变,CD31表达量明显升高(P<0.05),VEGF、Vav2、Rac1蛋白表达量显著升高(P<0.01)。与模型组相比,西药组足跖容积在第21天显著减小(P<0.01),膝关节滑膜组织病理改变明显改善,VEGF、Vav2表达量明显下降(P<0.05),Rac1蛋白表达量显著下降(P<0.01);电针组足跖容积在第21天显著减小(P<0.01),膝关节滑膜组织病理改变明显改善,VEGF、Rac1表达量明显下降(P<0.05),Vav2蛋白表达量显著下降(P<0.01)。结论电针改善RA的作用机制可能与抑制VEGF/Vav2/Rac1信号通路,进而抑制血管新生有关。

Increased IgG Rheumatoid Factor-Positivity in the Asian Rheumatoid Arthritis Patients Irrespective of Ethnicity

Aim of Work: Initial observations implied IgG rheumatoid factor (RF) to be common among Malaysian rheumatoid arthritis (RA) patients. We tested this hypothesis and used a multiethnic RA cohort (Malays, Chinese and Indians) to investigate whether the IgG RF predominance might be genetically or environmentally determined. Patients and Methods: 556 serum samples comprising 171 patients classified as RA according to the 1987 ACR criteria, 60 patients with other rheumatic diseases and 325 non-rheumatic controls were tested for IgG RF, IgM RF and anti-CCP by ELISA. The findings were then tested in a larger RA case-control cohort (n = 1844). Results: IgG RF predominated over IgM RF in all the investigated ethnic groups. The sensitivity, specificity, and diagnostic accuracy of IgG RF (55.6%, 91.2% and 80.2%, respectively) were superior compared to IgM RF, but comparable to anti-CCP. IgG RF was however, also increased in the Malaysian controls, but the IgG RF superiority over IgM RF was still apparent after cutoff adjustment according to the 1987 ACR criteria. Autoantibody levels did not differ between the three ethnic groups. The Receiver Operating Characteristics (ROC) curves showed larger areas under the curves for IgG RF (0.826) and for anti-CCP (0.867) than for IgM RF (0.737). Review of the literature showed consistently higher sensitivity for IgG RF in studies of Asian RA patients as compared to Caucasian and African-American studies. Conclusion: Increased frequency of IgG RF-positive in RA populations with different genetic background living in Malaysia argues for an environmental factor selectively amplifying the IgG RF response.

Diagnostic Value of Antibodies against a Modified Citrullinated Vimentin in Rheumatoid Arthritis

Aim of Work: To investigate the value of the detection of antibodies against modified citrullinated vimentin antibodies (anti-MCV) in comparison with anti-CCP2-for the diagnosis of rheumatoid arthritis (RA). Patients and Methods: The study Included Forty patients with Rheumatoid arthritis (RA). They under went assessment by the disease activity score (DAS-28), visual analogue scale (VAS) and health assessment questionnaire (HAQ). Thirty healthy subjects matched for age and sex served as a control group. Blood samples were obtained from patients and controls for erythrocyte sedimentation rate (ESR), C reactive protein (CRP), rheumatoid factor (RF). Anti-CCP2 and anti-MCV were determined using ELISA technique. Results: Estimated serum levels of anti-CCP2 and anti-MCV were significantly higher in patients compared to controls (p 0.001). There were no significant correlations between anti-MCV levels and age, dis- ease duration, duration of morning stiffness, number of swollen and tender joints, HAQ or ESR in patients with RA, while serum levels correlates significantly with DAS28, VAS and CRP (p 0.05). Anti-CCP2 correlates significantly with DAS28, VAS and CRP and ANA (p 0.05). Serum anti-MCV and anti-CCP2 were significantly correlated with each other (r = 0.483;p The receiver operating characteristic (ROC) curve was drawn and it showed that anti-MCV had diagnostic specificity, sensitivity of 93.3%, 75.5%, respectively, while anti-CCP2 specificity, sensitivity of 98.1%, 85%, respectively. Conclusion: Serum anti-MCV as well as the anti-CCP-2 assay perform comparably well in the diagnosis of RA. In the high-specificity range, however, the anti-CCP2 assay appears to be superior to the anti-MCV test.

Meta-Analysis on Efficacy and Safety of Modified Guizhi Shaoyao Zhimu Tang with the Western Medicines in Treating Rheumatoid Arthritis

Objective: To assess the efficacy and safety of modified Guizhi Shaoyao Zhimu Tang (GSZT) with the Western medicines in treating rheumatoid arthritis. Methods: All the relevant studies were collected by searching the Pubmed, Web of science, Embase, Cochrane Library, SpringerLink, China National Knowledge Infrastructure (CNKI), VIP Journals database, and Wanfang database from their inception to October 2017. After the assessment, the eligible ones were subject to Jadad score. The meta-analysis was conducted by RevMan 5.3 software. Results: Totally 10 randomized controlled trials (RCTs) involving 962 patients were enrolled. The clinical efficacy of analysis showed that modified GSZT with the Western medicines can significantly improve the clinical total effective rate [OR = 4.64, 95%CI (3.03, 7.12), P &minus;14.58, 95%CI (&minus;16.49, &minus;12.68), P &minus;12.62 95%CI (&minus;18.69, &minus;6.54), P &minus;49.88, 95%CI (&minus;77.6, &minus;22.09), P &minus;5.34, 95%CI (&minus;5.86, &minus;4.82), P < 0.001]. The adverse events had been seen in both of the two groups, however, the clinical symptoms of the group on modified GSZT with the Western medicines were obviously reduced than the other one [OR = 0.25, 95%CI (0.10, 0.61), Z = 3.06, P < 0.01]. This system review shows that the modified GSZT with the Western medicines improved the clinical efficacy, symptoms and the blood biochemical indicators were improved significantly than that of Western medicines alone on rheumatoid arthritis. At the same time, it can reduce adverse effects and enhance safety.

双能X射线吸收法诊断青海地区女性绝经后类风湿性关节炎患者骨质疏松症及其危险因素分析

目的:探讨双能X射线吸收法(DXA)诊断青海地区女性绝经后类风湿性关节炎(RA)患者发生骨质疏松症(OP)的危险因素。方法:选取2022年5月至2023年4月青海省中医院收治的200例绝经后女性RA患者,所有患者入院后均进行骨密度(BMD)检测,采用DXA测量腰椎L1~L4、腰整体、大转子、Ward's三角区、整体、前臂整体等部位。根据BMD检测结果,将患者各部位BMD的T值≤-2.5 SD纳入OP组(121例),BMD的T值>-2.5 SD纳入非OP组(79例)。对比分析两组RA患者不同部位的BMD的T值;采用受试者工作特征(ROC)曲线下面积(AUC)分析BMD的T值诊断OP效能;采用logistic回归法分析青海地区绝经后RA患者发生OP的危险因素。结果:OP组L1、L2、L3、L4、腰整体、大转子、Ward's三角区、整体及前臂整体BMD的T值均明显低于非OP组。ROC曲线分析中,L1、L2、L3、L4、腰整体、大转子、Ward's三角区、整体及前臂整体BMD的T值诊断OP的灵敏度分别为96.20%、95.22%、90.16%、96.03%、92.01%、89.36%、99.26%、90.02%和96.03%,特异度分别为81.00%、82.19%、85.22%、83.06%、83.06%、90.22%、80.06%、86.23%和83.09%,AUC分别为0.908、0.905、0.896、0.906、0.903、0.879、0.918、0.901和0.906。logistic回归分析中,高龄、病程长、28个关节的风湿活动度评分(DAS28)、血沉及补充钙剂等均为青海地区绝经后女性RA患者发生OP的危险因素。结论:DXA检测RA发生OP患者BMD可作为OP评估的“金标准”,且影响青海地区绝经后女性RA患者发生OP的危险因素较多,临床应结合相关因素制定合理的措施,以降低OP的发生率。

NLRC3通过抑制STING信号通路, 减轻类风湿关节炎患者巨噬细胞焦亡诱导的免疫炎症反应

目的探索含胱天蛋白酶激活和募集结构域核苷酸结合寡聚结构域样受体3(NLRC3)在RA患者巨噬细胞焦亡诱导的免疫炎症反应中的作用及潜在的机制。方法按照入组标准选取50名类风湿关节炎(RA)患者和10名健康志愿者,提取外周血巨噬细胞,根据分组要求进行转染处理,分为正常健康对照(NC)组、RA巨噬细胞模型(RA-MC)组、RA巨噬细胞模型联合NLRC3过表达(RA-MC联合pcDNA3.1-NLRC3)组、RA巨噬细胞模型联合NLRC3敲低(RA-MC联合siRNA-NLRC3)组、RA巨噬细胞模型联合干扰素基因刺激因子(STING)过表达(RA-MC联合pcDNA3.1-STING)组、RA巨噬细胞模型联合STING敲低(RA-MC联合siRNA-STING)组,采用透射电镜观察各组巨噬细胞焦亡的情况,实时定量PCR检测各组巨噬细胞中NLRC3、STING、胱天蛋白酶1(caspase-1)、消皮素D(GSDMD)的mRNA表达,ELISA测定各组巨噬细胞上清液中白细胞介素1β(IL-1β)、IL-18的水平。结果与NC组相比,RA-MC组中巨噬细胞表现出细胞焦亡的特点;与RA-MC组相比,RA-MC联合pcDNA3.1-NLRC3组和RA-MC联合siRNA-STING组中细胞焦亡情况改善,RA-MC联合siRNA-NLRC3组和RA-MC联合pcDNA3.1-STING组中细胞焦亡情况加重;与NC组相比,RA-MC组中STING、caspase-1、GSDMD的mRNA相对表达水平升高,炎症因子IL-1β、IL-18的水平也升高,而NLRC3的mRNA相对表达水平降低;与RA-MC组相比,RA-MC联合pcDNA3.1-NLRC3组和RA-MC联合siRNA-STING组中caspase-1、GSDMD的mRNA相对表达水平降低,炎症因子IL-1β、IL-18的水平也降低,RA-MC联合siRNA-NLRC3组和RA-MC联合pcDNA3.1-STING组的情况则与之相反;同样与RA-MC组相比,RA-MC联合pcDNA3.1-NLRC3组中STING的mRNA相对表达水平会降低,RA-MC联合siRNA-NLRC3组中STING的mRNA相对表达水平升高。结论NLRC3可通过抑制STING信号通路,减少caspase-1、GSDMD焦亡蛋白的产生,进而拮抗巨噬细胞焦亡,降低炎症因子IL-1β、IL-18的水平,从而减轻RA患者的免疫炎症反应。

新疆北疆地区类风湿关节炎患者中医证候分布规律及不同证型IL-1β、BMP6的差异性分析

目的:探究新疆北疆地区类风湿关节炎(RA)的中医证候分布规律及其与相关因子的内在关系,为类风湿关节炎的治疗提供帮助。方法:收集北疆地区类风湿关节炎患者217例,对其中医证型、舌苔、脉象、症状、病程、DAS28疾病活动度及用ELISA法测得的IL-1β、BMP6等指标进行统计分析。结果:RA患者女性多于男性,中医证型比例为寒湿痹阻证>肝肾不足证>痰瘀痹阻证>湿热痹阻证>风湿痹阻症>气血两虚证,不同中医证型RA患者性别、年龄分布无统计学差异(P>0.05),该地区RA患者主要证候特点以关节晨僵、关节痛有定处、关节疼痛喜按、遇寒痛增、阴雨天加重、日轻夜重、关节屈伸不利、腰膝酸软、肢体沉重等症状较为常见,不同证型间的病程、DAS28疾病活动度、C反应蛋白、BMP6存在统计学差异(P<0.05),IL-6、IL-1β、RF、抗环瓜氨酸多肽抗体不存在统计学差异(P>0.05)。与其他证型相比,风湿痹阻症的C反应蛋白高于肝肾不足证、寒湿痹阻证的DAS28疾病活动度水平高于肝肾不足证、湿热痹阻证的BMP6水平高于风湿痹阻证、寒湿痹阻证,痰瘀痹阻证BMP6水平高于风湿痹阻证。结论:新疆北疆地区的RA患者中医证候特点以“寒”“湿”“虚”为主,证型以寒湿痹阻证最为多见,且疾病活动度较高,湿热痹阻证及痰瘀痹阻证的骨关节异常表现较为突出,BMP6水平相对较高。年龄和性别对RA的发病有影响,病程长短对RA的中医证型分布有影响。

艾灸对实验性RA大鼠海马下丘脑垂体GR表达影响的研究

目的:在观察艾灸对实验性RA大鼠抗炎效应的基础上,研究艾灸对海马、下丘脑及垂体GR表达的影响,探索艾灸治疗RA的GR机制。方法:将雄性SD大鼠随机分为空白对照组、模型组、艾灸组,用福氏完全佐剂塑造大鼠实验性RA病理模型,艾灸"肾俞"、"足三里"治疗,测定大鼠右后足容积,采用免疫组化法检测海马、下丘脑、垂体GR表达。结果:造模后模型组大鼠足肿胀度明显高于空白对照组(P<0.01),艾灸组大鼠足肿胀度明显低于模型组(P<0.01);海马GR表达,模型组与空白组比较有增高趋势(P>0.05),艾灸组明显低于模型组(P<0.01);下丘脑GR表达,模型组明显高于空白对照组(P<0.01),艾灸组较模型组明显降低(P<0.01);垂体GR表达,模型组较空白对照组显著升高(P<0.01),而艾灸组与模型组比较无显著性差异(P>0.05)。结论:艾灸对实验性RA具有抗炎效应,艾灸对RA大鼠海马、下丘脑GR表达的调控可能是其实现抗炎效应的重要机制。

类风湿关节炎合并骨质疏松症分子信号通路机制的研究进展

骨质疏松症(OP)是类风湿关节炎(RA)最常见的共病之一。RA合并OP会加重骨破坏,增加骨折风险,降低患者的生活质量,增加社会负担。其病因复杂,发病机制尚不完全清楚。RA合并OP的治疗是目前临床工作的难点。了解疾病的信号通路,可以为疾病诊疗提供新的手段。该文对RA合并OP分子信号通路机制的研究进展作一综述。

抗CCP、抗AKA和抗RA33抗体检测在类风湿性关节炎诊断中的应用

目的探讨环瓜氨酸多肽(CCP)抗体、抗角蛋白抗体(AKA)、类风湿因子(RF)和抗RA33抗体对类风湿性关节炎(RA)的临床应用价值。方法88例RA患者和50例其他自身免疫病患者分别采用ELISA法检测抗CCP和抗RA33抗体,免疫荧光法检测抗AKA抗体,速率散射比浊法检测类风湿因子(RF),观察各指标对RA的诊断价值。结果患者抗CCP抗体、抗AKA抗体、抗RA33抗体和RF的敏感度分别为68.2,28.4,39.8和71.6,特异度为92.0,100,94.0和70.0;抗CCP抗体的检测阳性率高于抗AKA抗体和抗RA33抗体(P<0.01),与RF无统计学显著性差异(P=0.622)。三种抗体对RF阴性组RA诊断的阳性率为63.0,37,44.4,与RF阳性组RA阳性率70.5,24.6,37.7相比较,两组差异无统计学意义(P>0.05)。结论抗CCP,抗AKA,抗RA33抗体均是RA诊断的特异性指标,对诊断RF阴性RA具有较高敏感度和特异度,将上述抗体与RF进行联合检测,有助于RA的早期诊断。

艾灸调整实验性RA大鼠HPAA功能的GR机制研究

目的:探索艾灸调整实验性类风湿性关节炎(RA)大鼠下丘脑-垂体-肾上腺轴(HPAA)功能的糖皮质激素受体(GR)机制。方法:将SD大鼠随机分为空白对照组、模型组、艾灸组、艾灸加注射RU28362组,用福氏完全佐剂塑造实验性RA病理模型,以GR激动剂RU28362腹腔注射作为干预研究手段,艾灸"肾俞"、"足三里"穴治疗,检测大鼠足容积,用ELISA法测定大鼠血浆CRH、ACTH、GC含量。结果:模型组大鼠足肿胀度明显高于空白对照组(P<0.01),艾灸组大鼠足肿胀度明显低于模型组(P<0.01),艾灸加注射RU28362组足肿胀度与模型组比较无显著性差异(P>0.05);与空白组对照组比较,模型组血浆CRH、GC含量显著增高(P<0.01),ACTH含量显著降低(P<0.05);艾灸组血浆CRH、GC含量明显低于模型组(P<0.01),ACTH含量明显高于模型组(P<0.05),但艾灸加注射RU28362组血浆CRH、ACTH、GC含量与模型组比较无显著性差异(P>0.05)。结论:艾灸对实验性RA具有明显的抗炎效应;艾灸对实验性RA大鼠的HPAA功能紊乱有良性调整作用;海马GR在艾灸调整实验性RA大鼠HPAA功能中具有重要作用。

不同刺灸法调节RA细胞因子的实验研究进展

细胞因子水平异常是RA重要发病机理,针灸治疗RA疗效显著,研究表明,针灸良性调节RA异常的细胞因子是发挥治疗效应的关键所在。笔者检索了近10年相关文献并整理、综述、分析不同刺灸法对RA发生特异改变的不同细胞因子的影响。在此基础上通过比较阐释针灸治疗RA的有效方法,并评述该领域实验研究存在的问题,为今后深入研究提供参考和依据。

辅助T细胞多巴胺受体(DR)表达对类风湿关节炎(RA)患者疾病活动度的影响

目的 检测类风湿关节炎（rheumatoid arthritis,RA）患者外周血辅助T淋巴细胞（T helper cells,Th cells）不同亚群细胞膜表面多巴胺受体（dopamine receptor,DR）水平,分析其与疾病活动度、实验室指标及功能状态之间的关系。方法 选取25位初诊或3个月内未接受DMARDs治疗的RA患者（DAS28〉3.2）,12位健康对照及13位同期年龄匹配的骨关节炎（osteoarthritis,OA）患者。采用流式细胞术检测患者外周血Th细胞亚群表面DR1~DR5的表达情况,分析Th细胞DR表达水平与人口学资料、实验室检查、功能状态及疾病活动度之间的相关性。结果 RA组Th2细胞百分比为1.28%（0.74%~2.68%）,较健康对照组（中位数0.18%,四分位数间距0.11%~0.31%,P〈0.001）及OA组（中位数0.48%,四分位数间距0.03%~1.47%,P=0.029）明显升高。RA组Th2细胞DR2表达水平为25.40%（四分位数间距3.79%~37.10%）,明显高于健康对照组（中位数3.74%,四分位数间距0.00%~12.98%,P=0.006）及OA组（中位数3.45%,四分位数间距0.00%~20.55%,P=0.040）。RA组Th2细胞DR4表达量也高于健康对照组和OA组（健康对照组vs.RA组,P=0.022;OA组vs.组,P=0.010）。Th2细胞与关节肿胀数（swollen joint count,SJC）和简化疾病活动指数（SDAI）呈正相关（分别为r=0.421,P=0.036;r=0.396,P=0.050）。Th1细胞DR5百分比分别为2.22%（四分位数间距0.57%~12.24%）与SJC及临床疾病活动指数（CDAI）呈正相关（分别为r=0.492,P=0.012;r=0.445,P=0.026）。Th2细胞DR1和DR3百分比分别为11.15%（四分位数间距2.93%~36.20%）、9.80%（1.62%~23.05%）,均与健康评估问卷（Health Assessment Questionnaire,HAQ）评分呈负相关（分别为r=-0.469,P=0.018;r=-0.464,P=0.019）。结论 RA患者Th2细胞多巴胺受体DR2和DR4明显升高,Th细胞DR水平与RA患者SJC、CDAI及HAQ存在相关性。

铁死亡诱导剂咪唑酮埃拉斯汀(IKE)通过抑制IL-6、CCL5及CXCL9分泌缓解CIA小鼠的肺纤维化

目的 探索铁死亡诱导剂咪唑酮埃拉斯汀(IKE)对胶原蛋白诱发关节炎(CIA)小鼠肺纤维化的作用及潜在机制。方法 选取8周龄~10周龄DBA/1小鼠,按照完全Freund佐剂(CFA)与鸡Ⅱ型胶原蛋白混合乳化方法建立CIA小鼠模型,设置对照组、 CIA组、 CIA联合IKE组。每2 d进行关节评分与爪垫厚度测量,39 d后收集小鼠各脏器组织。HE染色、番红-固绿染色、甲苯胺蓝染色评价关节处组织病理改变;Masson染色评价肺部组织病理改变。免疫组织化学染色法检测肺组织α平滑肌肌动蛋白(α-SMA)、成纤维细胞活化蛋白α(FAPα)、转化生长因子β(TGF-β)及Ⅰ型胶原蛋白(Col1)、白细胞介素1(IL-1)、 IL-6、 IL-17及肿瘤坏死因子α(TNF-α)的表达水平;Olink mouse exploratory panel检测小鼠血清细胞因子IL-17α、 IL-17F、 TGF-β1、整合素亚基β6(ITG-β6)、 TNF受体超家族成员11B(TNFRSF11b)、 TNF受体超家族成员12A (TNFRSF12a)、 IL-6、 IL-1α、 IL-1β、 IL-10、 TNF-α、 CC趋化因子配体5(CCL5)、 CCL2、 CXC趋化因子配体9(CXCL9)、 CXCL1、烟酰胺腺嘌呤二核苷酸激酶(NADK)、促红细胞生成素(EPO)、集落刺激因子2(CSF2)、 TGF-α、 CCL20、 CCL3水平。结果 与CIA组相比,CIA联合IKE组治疗后关节炎症及关节损伤明显缓解;肺组织α-SMA、 FAPα、 TGF-β和Col1表达水平均呈下降趋势,表明CIA小鼠肺部胶原蛋白聚集减少,组织病变明显缓解;IL-6、 CCL5、 CXCL9、 IL-6水平显著下降表明CIA小鼠肺部炎症显著缓解。结论 IKE除缓解CIA小鼠关节炎症及关节损伤外,还可通过抑制IL-6、 CCL5及CXCL9表达缓解CIA伴发的肺纤维化。

类风湿性关节炎与IL-1/IL-1Ra平衡关系的研究进展

类风湿性关节炎(RA)为常见的自身免疫疾病,其发生、发展与众多炎性因子相关,白细胞介素1(IL-1)是一种炎症反应的重要介质,在人体的自然反应和病理条件导致慢性炎症的发展中都有重要作用,然而在抗炎细胞因子的影响下,体外IL-1炎症作用可以被一个特别强大的抑制剂——IL-1受体拮抗剂(IL-1Ra)抑制或者消除。目前研究显示,IL-1通过与Ⅰ型IL-1受体结合,可激活系列信号转导通路进而诱发关节软骨和骨侵蚀,同时可诱导其他炎性因子表达,协同加剧关节破坏,而IL-1Ra可牢固结合Ⅰ型IL-1受体,抑制IL-1的生物学效应,因此,RA患者体内IL-1/IL-1Ra的动态平衡对于该病的转归至关重要。深入对RA发病中IL-1/IL-1Ra平衡的认识对该病的预防、治疗及转归具有重要作用。