镇关灵治疗类风湿性关节炎的药效学研究

目的 探索镇关灵治疗类风湿性关节炎(rheumatoida~dtis，RA)的作用。方法 以佐剂性关节炎(AA)、蛋清性关节炎、角叉菜胶性关节炎为实验病理目标，建立二硝基氟苯所致小鼠迟发型超敏反应(DTH)、棉球肉芽肿及醋酸所致小鼠腹腔毛细血管通透性增高和扭体反应等病理模型。结果 镇关灵能显著抑制大鼠佐剂性关节炎、蛋清性关节炎、角又菜胶所致炎症的足跖肿胀度和棉球肉芽肿，抑制由醋酸引起的小鼠扭体反应和腹腔毛细血管通透性增高，并可抑制DTH。结论 镇关灵具有良好的抗炎镇痛免疫抑制作用，对类风湿性关节炎具有明显的预防和治疗作用。     

骨湿宁治疗风湿性关节炎的实验研究

目的:观察骨湿宁的主要药理作用。方法:采用佐剂、角叉菜胶、尿酸钠等引发大鼠关节炎症或疼痛模型、小鼠热板、醋酸扭体法以及腹腔毛细血管通透性来评价骨湿宁的抗炎、镇痛作用。结果:骨湿宁能抑制大鼠佐剂性关节炎的原发性和继发性病变;抑制角叉菜胶所致的大鼠炎症肿胀;对由大鼠尿酸钠关节炎致痛、小鼠热板、醋酸扭体致痛均有明显的镇痛作用;并具有降低小鼠腹腔毛细血管通透性、抑制大鼠棉球致组织增生的作用。结论:骨湿宁具有一定的抗炎、镇痛作用     

前列宁栓抗炎镇痛作用实验

目的:研究前列宁栓的抗炎、镇痛作用。方法:采用二甲苯所致小鼠耳廓肿胀实验、角叉菜胶致大鼠足跖肿实验、大鼠棉球肉芽肿的影响实验、小鼠腹腔毛细血管通透性实验,细菌性(大肠杆菌)前列腺炎的抗炎作用。采用醋酸致小鼠扭体反应实验和小鼠热板法实验观察了前列宁栓的镇痛作用。结果:前列宁栓可明显抑制二甲苯所致的小鼠耳廓炎症;在多数时间降低角叉菜胶致大鼠足跖肿胀;明显抑制大鼠棉球肉芽肿的生成;明显降低小鼠腹腔毛细血管通透性;明显抑制大鼠细菌性前列腺炎;明显降低醋酸致小鼠扭体反应数;明显升高小鼠痛阈值。结论:前列宁栓具有明显的抗炎、镇痛作用。     

骨湿宁治疗风湿性关节炎的实验研究

目的：观察骨湿宁的主要药理作用。方法：采用佐剂，角叉菜胶，尿酸钠等引发大鼠关节炎症或疼痛模型，小鼠热板，醋酸扭体法以及腹腔毛细血管通透性来评价骨湿宁的抗炎，镇痛作用。结果：骨湿宁能抑制大鼠佐剂性关系炎的原发性和继发性病变；抑制角叉菜胶所致的大鼠炎症肿胀；对由大鼠尿酸钠关节炎致痛，小鼠热板，醋酸扭体致痛均有明显的镇痛作用；并具有降低小鼠腹腔毛细血管通透性，抑制大鼠棉球致组织增生的作用。结论：骨湿宁具有一定的抗炎，镇痛作用。     

乙醇提取新鲜当归油的抗炎镇痛作用

目的 :研究当归油的镇痛、抗炎作用。方法 :应用二甲苯致小鼠耳廓肿胀、醋酸致小鼠腹腔毛细血管通透性增高、蛋清致大鼠足跖肿胀及大鼠棉球肉芽肿增生4种动物模型进行抗炎药效学实验 ;采用醋酸致小鼠扭体反应 ,进行镇痛实验。结果 :当归油能显著抑制上述各种动物模型的炎症反应及醋酸引起的小鼠扭体反应。结论 :当归油对急、慢性炎症均有明显抑制作用 ,且有一定的镇痛效果。     

福建穿山龙抗炎镇痛作用的实验研究

运用二甲苯、角叉菜胶致炎、小鼠扭体反应等实验观察。福建穿山龙ｉｇ能明显抑制二甲苯引起的小鼠耳壳炎症、大鼠角叉菜胶性足关节肿胀,降低小鼠腹腔毛细血管通透性及明显抑制大鼠棉球肉芽肿;并能延长小鼠疼痛反应时间,减少小鼠扭体反应次数。实验结果表明,福建穿山龙具有明显的抗炎、镇痛作用。     

大火草抗慢性前列腺炎作用研究

目的验证大火草抗慢性前列腺炎作用。方法采用二甲苯致小鼠耳肿胀法、小鼠腹腔毛细血管通透性法、小鼠棉球肉芽肿法、角叉菜胶致大鼠慢性非细菌性前列腺炎法。结果大火草对二甲苯所致小鼠炎症、醋酸所致小鼠腹腔毛细血管通透性的增加、小鼠棉球肉芽肿、角叉菜胶所致大鼠非细菌性前列腺炎均有抑制作用,与模型组比较,差异有统计学意义。结论大火草具有明显抑制前列腺炎的作用。     

山桔叶醇提物抗炎镇痛作用的研究

目的 观察山桔叶醇提物(GPE)对小鼠的抗炎镇痛作用.方法 通过二甲苯致小鼠耳廓肿胀、0.6％冰乙酸致小鼠腹腔毛细血管通透性、1％角叉菜胶致小鼠足肿胀及用小鼠棉球肉芽肿法观察GPE的抗炎作用;通过冰乙酸致小鼠扭体反应和热板致小鼠疼痛法观察GPE的镇痛作用.结果 GPE高、中、低剂量均可显著抑制二甲苯致小鼠耳廓肿胀的肿胀度、1％角叉菜胶致小鼠的足肿胀、0.7％冰乙酸致小鼠的扭体反应次数;GPE高、低剂量可显著抑制冰乙酸致小鼠腹腔毛细血管通透性的增高;GPE高、中剂量均可抑制角叉菜胶致小鼠足肿胀中PGE2的渗出及小鼠棉球肉芽肿的重量,可增高热板致小鼠疼痛的痛阈值.结论 GPE对小鼠有抗炎镇痛的作用.     

白族药紫地榆体内镇痛抗炎作用初步研究

目的：初步观察紫地榆的体内镇痛、抗炎作用。方法：采用醋酸扭体法观察紫地榆镇痛作用,采用二甲苯致小鼠耳肿胀法,醋酸致小鼠腹腔毛细血管通透性增加,小鼠棉球肉芽肿法观察紫地榆的抗炎作用。结果：抗炎实验中,与对照组比较,紫地榆高、中、低剂量组均可明显抑制二甲苯所致小鼠耳廓的肿胀度,抑制醋酸引起的小鼠毛细血管通透性增加;与模型组比较,紫地榆能减轻小鼠棉球肉芽肿质量。镇痛实验中,与对照组比较,紫地榆可延缓醋酸所致小鼠扭体反应的潜伏期,减少扭体反应次数。结论：紫地榆提具有明显的体内抗炎镇痛作用。     

合成鱼腥草素的抗炎镇痛作用

合成鱼腥草素灌胃给药对巴豆油致小鼠耳肿胀、角叉菜胶致大鼠足肿胀、醋酸致小鼠腹腔毛细血管通透性增高均有显著抑制作用．同时灌胃给药可以抑制醋酸所致的小鼠扭体反应，延长热痛反应潜伏期，拮抗甲醛致痛作用     

Pharmacological blockade of CCR1 ameliorates murine arthritis and alters cytokine networks in vivo

BACKGROUND AND PURPOSE: The chemokine receptor CCR1 is a potential target for the treatment of rheumatoid arthritis. To explore the impact of CCR1 blockade in experimental arthritis and the underlying mechanisms, we used J-113863, a non-peptide antagonist of the mouse receptor. EXPERIMENTAL APPROACH: Compound J-113863 was tested in collagen-induced arthritis (CIA) and three models of acute inflammation; Staphylococcus enterotoxin B (SEB)-induced interleukin-2 (IL-2), delayed-type hypersensitivity (DTH) response, and lipopolysaccharide (LPS)-induced tumour necrosis factoralpha (TNFalpha) production. In the LPS model, CCR1 knockout, adrenalectomised, or IL-10-depleted mice were also used. Production of TNFalpha by mouse macrophages and human synovial membrane samples in vitro were also studied. KEY RESULTS: Treatment of arthritic mice with J-113863 improved paw inflammation and joint damage, and dramatically decreased cell infiltration into joints. The compound did not inhibit IL-2 or DTH, but reduced plasma TNFalpha levels in LPS-treated mice. Surprisingly, CCR1 knockout mice produced more TNFalpha than controls in response to LPS, and J-113863 decreased TNFalpha also in CCR1 null mice, indicating that its effect was unrelated to CCR1. Adrenalectomy or neutralisation of IL-10 did not prevent inhibition of TNFalpha production by J-113863. The compound did not inhibit mouse TNFalpha in vitro, but did induce a trend towards increased TNFalpha release in cells from synovial membranes of rheumatoid arthritis patients. CONCLUSIONS AND IMPLICATIONS: CCR1 blockade improves the development of CIA, probably via inhibition of inflammatory cell recruitment. However, results from both CCR1-deficient mice and human synovial membranes suggest that, in some experimental settings, blocking CCR1 could enhance TNF production.     

Development of a delayed-type hypersensitivity granuloma model in the mouse for the study of chronic immune-mediated inflammatory disease

A cutaneous model of delayed-type hypersensitivity granuloma (DTH GRA) was developed, using methylated bovine serum albumin (mBSA) which could be easily quantified and represented chronic cellular immune-mediated inflammation characteristic of rheumatoid arthritis (RA). Quantitative kinetics showed maximal DTH GRA "wet" tissue weights at d.5 post-induction, diminishing between d.15-22; DTH GRA "dry" tissue weights peaked between d.8-22. Histological evaluation revealed early extensive fibrin deposition, edema, mixed PMN/mononuclear leucocyte infiltration and angiogenesis (d.2-5), followed by increased macrophage recruitment, lymphocyte infiltration, angiogenesis and vasculitis (d.10-15). Fibrin resorption and replacement by fibrous tissue resulted in resolution by d.35. It is suggested that the DTH GRA reaction represents a relevant model for probing pathogenic mechanisms and potential therapeutics for RA.     

Comparative investigations of various immunoregulatory substances in the delayed type hypersensitivity test of the mouse

The substances D-penicillamine, auranofin, chloroquine, levamisole, BM 41.332, azimexone, bestatin, methisoprinol (inosiplex), thymosine (fraction 5), indomethacin and cyclophosphamide were examined comparatively in the delayed type hypersensitivity test after oxazolone sensitisation in mice. It was found, that only the basal antirheumatic drugs D-penicillamine, auranofin, chloroquine and levamisole and also BM 41.332 led to a potentiation of the DTH reactions. Methisoprinol, bestatin, azimexone, thymosine fraction 5 and indomethacin had no effect on the DTH, whilst the immunosuppressant cyclophosphamide led to an inhibition of the DTH reaction. It is concluded that this pharmacological model is suitable for screening of new basal drugs for rheumatoid arthritis.     

Does the p38 MAP kinase inhibitor pamapimod have potential for the treatment of rheumatoid arthritis?

Methotrexate alone or in combination with other agents is the standard treatment for moderate-to-severe rheumatoid arthritis. As biological agents are expensive, they are not usually used until methotrexate has failed to give a good response. Thus, there is scope for the development of cheaper drugs that can be used instead of methotrexate or in addition to methotrexate. Pamapimod is a p38α inhibitor being developed for use in the treatment of rheumatoid arthritis. The objective of this review was to evaluate the recent clinical trials of pamapimod in subjects with rheumatoid arthritis. There is no clear-cut evidence that pamapimod alone or in the presence of methotrexate is efficacious in subjects with rheumatoid arthritis but it does cause adverse effects. It is unlikely that pamapimod will be useful in the treatment of rheumatoid arthritis.     

对幼年型类风湿性关节炎误诊的思考

目的探讨导致幼年型类风湿性关节炎误诊的常见原因。方法回顾性分析7年来经治的21例误诊为其他疾病的幼年型类风湿性关节炎病例。结果21例患者中，误诊为化脓性关节炎10例，结核性关节炎5例，强直性脊柱炎3例，风湿热3例。结论幼年型类风湿性关节炎在临床上极易误诊，需提高对此病的警惕性，早期做出正确诊断。     

类风湿性关节炎可溶性细胞因子的临床实验分析

目的：分析三种可溶性细胞因子受体（sIL-2R,sIL-6R,sTNFRI）对类风湿性关节炎的影响。方法：用ELISA方法测定了21例类风湿性关节炎患者血清中三种可溶性细胞因子受体的含量,并与其他指标进行了对比分析。结果：21例类风湿性关节炎患者的sIL-2R、sIL－6R和sTNFRI的水平显著升高（P〈0．01）。结论：三种可溶性细胞因子受体与类风湿性关节炎具有密切的关系,可作为临床监控指标;且具有一定的临床意义。     

Immunopharmacologic studies of D-penicillamine-L-cysteine disulfide

Effects of D-penicillamine-L-cysteine disulfide (P-C) on some immunological parameters were examined in normal and immunity-impaired mice and rats. P-C enhanced the DNA synthesis in concanavalin A-stimulated mouse spleen cell cultures in vitro. In vivo, administration of P-C produced either enhancement or depression of plaque forming cell (PFC) response and delayed type hypersensitivity (DTH) to sheep red blood cells (SRBC) in low responder mice to SRBC, depending on the dose of P-C. P-C restored the impaired PFC response in hydrocortisone-pretreated mice. The enhancing effect of P-C was not shown in high responder mice to SRBC, but an inhibiting effect was observed. P-C inhibited the suppressor cell induction on PFC response in mice immunized with a supraoptimum dose of antigen. In adjuvant arthritic rats, P-C induced severe arthritis by eliminating the suppressor cells regulating this disease process. The relevance of these findings and mode of action of D-penicillamine in rheumatoid arthritis is discussed.     

Do antivirals have any utility in the treatment of arthritis?

Viruses have been linked to arthritides by several pathways. Apart from the ability of different viral pathogens to cause arthritic symptoms directly, only some circumstantial evidence for the involvement of (retro)viruses in the pathogenesis of rheumatoid arthritis has been presented in recent years. Therefore, the question of whether antiviral agents can be used to treat arthritis has become of interest. However, the mechanisms by which exogenous retroviral infection as well as activation of endogenous retroviral sequences may potentially lead to the induction of rheumatoid arthritis is just beginning to emerge. Moreover, the hypothesis that persistent viral infection may account for some hitherto unclassified, chronic arthritides, still needs to be confirmed. Therefore, the use of antiviral agents in the treatment of arthritides has been limited to viral complications of anti-arthritic therapy and to some experimental approaches. In this review, we will focus on current concepts of viral involvement in arthritis and point to future directions in the use of antiviral agents for arthritis.     

抗CCP抗体在类风湿关节炎早期诊断中的意义及对MTX治疗反应的评价

目的检测环瓜氨酸多肽(CCP)抗体在类风湿关节炎(RA)中的敏感性和特异性,以探讨抗CCP抗体对类风湿关节炎早期诊断的意义;同时观察甲氨喋呤(MTX)治疗抗CCP抗体阳性早期RA患者的疗效。方法应用ELISA法检测69份人血清的抗CCP抗体的表达情况,并比较抗CCP抗体与类风湿因子、C反应蛋白、血沉等指标间的相关性。对于抗CCP抗体阳性的早期RA患者,应用MTX(10mg/次,1次/周),治疗6个月后,观察效果。结果抗CCP抗体对RA的敏感性为74.91%,特异性为94.74%。RF对RA的敏感性为77.42%,与抗CCP抗体无显著性差异,特异性为76.31%,显著低于抗CCP抗体(P<0.05)。早期RA患者抗CCP抗体的阳性率与中晚期RA患者的抗CCP抗体阳性率分别为61.54%和83.33%,无显著性差异(P>0.05)。抗CCP抗体与RF、ESR有相关性(P<0.05),而与CRP、免疫球蛋白等无相关性(P>0.05)。MTX治疗6个月后,抗CCP抗体阳性的早期RA患者改善率为50%。结论抗CCP抗体对RA具有良好的敏感性和很高的特异性,在RA的早期可以出现,对RA的早期诊断具有重要意义。联合检测抗CCP抗体、RF及其他实验室指标,可以提高抗CCP抗体的临床应用价值。MTX治疗抗CCP抗体阳性的早期RA患者,短期疗效较好。由于本组例数较少,仍需进一步探讨、观察。