T细胞免疫核糖核酸治疗大鼠佐剂关节炎的研究

目的 探讨Ｔ细胞核糖酸（ｉＲＮＡ）是否可以通过调节机体免疫功能而影响关节炎病理生理过程，为类风湿关节炎治疗探索一条新路。方法 利用大鼠佐剂性关节炎（ＡＡ）动物模型，腹腔注射Ｔ细胞免疫核糖核酸，观察关节体积、关节指数及关节病理变化。结果 注射１０ｄ后，关节体积、关节指数与关节炎对照组比较差异均有显著性（Ｐ〈０．０５），病理结果显示滑膜组织增生及炎症细胞浸润均较关节炎对照组明显减轻。结论 Ｔ细胞ｉＲＮ     

日本血吸虫免疫核糖核酸佐剂作用的研究

本实验研究了日本血吸虫免疫核糖核酸（ＳｉＲＮＡ）的佐剂作用。用ＥＬＩＳＡ检测结果表明，用ＳｉＲＮＡ加日本血吸虫成虫抗原（ＳＷＡ）免疫的小鼠的抗体水平显著高于仅用ＳｉＲＮＡ或ＳＷＡ免疫的小鼠。尾蚴攻击感后，用ＳｉＲＮＡ＋ＳＷＡ或ＳｉＲＮＡ免疫的小鼠有较高的减虫率，两组间减虫率无显著性差异。这些结果表明，ＳｉＲＮＡ能增强宿主的体液免疫反应，但未能增强宿主保护性免疫力。     

白芷总挥发油对大鼠佐剂性关节炎的影响

目的探讨白芷总挥发油(EOAD)对完全弗氏佐剂(CFA)诱导大鼠佐剂性关节炎的治疗作用,并探讨其作用机制。方法 Wistar大鼠随机分为空白对照组、模型组、地塞米松组(5 mg/kg)、EOAD低剂量组(70 mg/kg)和高剂量组(140 mg/kg)。除空白对照组外,各组大鼠足趾皮内注射CFA诱导佐剂性关节炎模型,于造模第15天起连续给药7 d,观察EOAD对大鼠体重、足肿胀及脏器指数的影响;检测佐剂性关节炎大鼠血清中肿瘤坏死因子(TNF)-α、前列腺素(PG)E2、一氧化氮(NO)含量及一氧化氮合酶(NOS)活力。结果与空白对照组比较,模型组大鼠体重增长缓慢,足肿胀明显,关节炎评分增加,胸腺和脾指数明显增加,血清中NO、PGE2和TNF-α含量及NOS活力均明显升高(P0.05或P0.01)。与模型组比较,EOAD治疗可显著减轻佐剂性关节炎大鼠右后足的足肿胀(P0.05),降低关节炎评分,并使大鼠体重及脏器指数增加,同时明显降低血清中NOS活力和NO、TNF-α、PGE2的含量(P0.01)。结论 EOAD对大鼠佐剂性关节炎有显著抑制作用,其作用机制可能与降低血清炎症细胞因子TNF-α,PGE2水平及NOS活力有关。     

溴隐亭对大鼠佐剂关节炎的影响

目的 观察溴隐亭对大鼠佐剂关节炎的影响。方法 取Ｗｉｓｔａｒ维性大鼠；分为三组，第一组为对照组；第二组单纯给予完全佛氏佐剂（ＦＣＡ）皮内注射，透发佐剂关节炎（ＡＡ）；第三级在给予ＦＣＡ前三天开始给予溴隐亭灌胃，连续７ｄ，就各组分别观察ＡＡ的发生率，右后肢脚容量的变化，并对癌发病进行 发。结果 第三组与第二组比较，不仅ＡＡ的发病率明显降低（２０％，６０％）变化，并对继发病进行评分。结果 第三组与第二     

葡萄糖胺软骨素与黄芩联合对佐剂性关节炎大鼠血清PGE2影响的实验研究

类风湿性关节炎（rheumatoid arthritis，RA）是一种慢性炎症性疾病，目前尚无理想的治疗药物，因此研制疗效好、副作用小的抗类风湿性关节炎药物一直是人们关注的焦点。葡萄糖胺软骨素（Glueosamine ChondroitJn,GC）是一种目前在国外较受关注的抗类风湿新药，而黄芩（SB）既具有较强的抗炎作用。同时又具有低毒的特性。本文旨在研究这两种药物联合应用对大鼠佐剂性关节炎（AA）的协同治疗作用。     

Ⅱ型胶原蛋白对大鼠佐剂性关节炎的抑制作用

目的　观察Ⅱ型胶原蛋白 (CⅡ )对大鼠佐剂性关节炎 (AA)的影响及给药时间与疗效之间的关系。方法　用完全福氏佐剂 (CFA)致SD大鼠AA ,分别于致关节炎之前 2周、同时及之后 2周开始给予不同剂量CⅡ灌胃 ,均持续 3个月 ;分别观察大鼠AA的发生率及晚期致畸情况 ,并对继发病情评分。结果　与对照组比较 ,给予CⅡ灌胃的SD大鼠 ,其AA的发病率及晚期致肢体畸形比例明显降低 (5 8 9%～ 6 5 8%∶90 0 % ;30 %～ 40 %∶10 0 % ) ,而且关节炎症明显减轻 ,病程缩短 [(35±31)～ (45± 37) ]d∶(10 8± 15 )d ,病程中关节外表现亦减少 (30 0 %～ 36 7%∶10 0 % ) ;其中 ,以致AA前 2周开始治疗的CⅡ Ⅰ组疗效更好。结论　CⅡ灌胃对大鼠AA的原发及继发病变均有良好的治疗作用 ;预防性用药 ,疗效更佳。此结果为CⅡ用于人类类风湿关节炎的治疗提供了动物实验依据。     

口服Ⅱ型胶原蛋白诱导佐剂性关节炎大鼠免疫耐受的研究

目的：对口服可溶性Ⅱ型胶原蛋白（typeⅡcollagen，CⅡ）诱导佐剂性关节炎（adju-vantarthritis，AA）大鼠免疫耐受的治疗作用及其机制进行研究，并与雷公藤多甙的疗效进行比较。方法：建立大鼠AA模型，观察其口服CⅡ雷公藤多甙后关节肿胀度及病理学变化；检测相关的免疫学指标，包括迟发型超敏反应、循环免疫复合物、血清中抗CⅡ抗体的抗结核杆菌抗体水平。结果：①口服CⅡ能缓解AA大鼠的四肢关节症状和全身症状，减轻关节腔内滑膜增生及炎细胞浸润，效果较雷公藤多甙显著。②口服CⅡ使AA大鼠迟发型超敏反应减弱，循环免疫复合物及血清中抗CⅡ抗体水平降低。结论：口服CⅡ对AA大鼠有明显的近期治疗效果，其作用机制可能与抑制Th1细胞介导的细胞免疫，增强Th2细胞介导的体液免疫有关。     

溴隐亭对大鼠佐剂关节炎的影响

目的　观察溴隐亭对大鼠佐剂关节炎的影响。方法　取Wistar雄性大鼠 ,分为三组 ,第一组为对照组 ;第二组单纯给予完全佛氏佐剂 (FCA)皮内注射 ,诱发佐剂关节炎 (AA) ;第三组在给予FCA前三天开始给予溴隐亭灌胃 ,连续 7d ,就各组分别观察AA的发生率 ,右后肢脚容量的变化 ,并对继发病进行评分。结果　第三组与第二组比较 ,不仅AA的发病率明显降低 (2 0 %∶6 0 % ) ,而且关节的炎症反应程度及继发病变的评分在两组间均有显著差异。结论　溴隐亭对大鼠佐剂关节炎的原发及继发病变均有抑制作用 ,为临床类风湿关节炎的治疗提供了新的思路。     

全身调控一氧化氮水平对大鼠佐剂性关节炎的影响

类风湿关节炎 (ｒｈｅｕｍａｔｏｉｄａｒｔｈｒｉｔｉｓ,ＲＡ)的发病机制较为复杂 ,目前还不十分清楚。Ｆａｒｒｅｌｌ等[1] 发现ＲＡ患者血清及关节液中一氧化氮 (ＮＯ)含量增高 ,提示ＮＯ与ＲＡ的发病密切相关。本实验通过建立大鼠佐剂性关节炎 (ＡＡ)模型 ,观察全身调控ＮＯ水平对多发性关节炎的影响 ,旨在探讨ＮＯ对关节炎症的作用机制 ,为防治ＲＡ提供实验依据。1　材料与方法1 1　主要试剂不完全福氏佐剂及诱导型一氧化氮合酶 (ｉＮＯＳ)抑制剂Ｌ ＮＡＭＥ为美国Ｓｉｇｍａ公司产品。卡介苗为卫生部成都生物制品研究所产品。ＮＯ试剂…     

Incadronate在大白鼠佐剂性关节炎中的关节保护作用

目的 研究二膦酸盐对大白鼠佐剂性关节炎的关节炎症、肿胀以及结构破坏的治疗作用。方法 40只雌性Lewis大白鼠随机分为5组，其中4组通过接种乳酪分枝杆菌诱发关节炎。取接种组中3组自接种后15～42d给予incadronate不同剂量每日1次皮下注射。通过观测关节炎表现，并结合放射学和组织学等方法，分析药物的治疗作用。结果 在incadronate的三种治疗剂量中，大剂量组较小剂量组对关节炎症的抑制作用和关节的保护作用更强。组织学显示，经药物治疗，关节软骨及其下面的骨质结构得到保护；破骨细胞数量减少，并呈现出功能不活跃的彤态。结论 Incadronate可抑制大白鼠佐剂性关节炎的关节炎症、肿胀，保护关节软骨及其下面的骨质结构。提示二膦酸盐类药物可作为类风湿关节炎的辅助治疗药物。     

青藤碱对佐剂性关节炎大鼠腹腔巨噬细胞表达细胞因子的影响

目的　观察不同剂量的青藤碱体外作用对佐剂性关节炎 (AA)大鼠腹腔巨噬细胞核因子 κB (NF κB)活性及肿瘤坏死因子 (TNF) αmRNA、白细胞介素 (IL) 1βmRNA、IL 10mRNA的影响 ,以阐明该药抗炎和抗风湿的可能机制。方法　以佐剂性关节炎大鼠为模型 ,收集腹腔巨噬细胞 ,电泳迁移率改变分析法 (EMSA)测NF κB活性 ,反转录 多聚酶链反应 (RT PCR )测TNF αmRNA、IL 1βmRNA、IL 10mRNA的表达。 结果　佐剂性关节炎后腹腔巨噬细胞内NF κB活性与TNF αmRNA、IL 1βmRNA、IL 10mRNA的表达与正常对照相比均显著升高 (P <0 0 5 ) ,青藤碱在一定的浓度范围内抑制NF κB活性与TNF αmRNA、IL 1βmRNA、IL 10mRNA的表达。腹腔巨噬细胞NF κB的变化趋势与TNF αmRNA、IL 1βmRNA、IL 10mRNA的表达呈正相关。 结论　青藤碱通过下调NF κB活性而降低腹腔巨噬细胞内TNF αmRNA、IL 1βmRNA的表达。     

核因子κB在佐剂性关节炎大鼠肺组织中的表达

目的　研究核因子κB (NF κB)在佐剂性关节炎 (AA)大鼠肺组织中的表达 ,以探讨类风湿肺的发病机制。方法　通过给大鼠右后足足跖部皮下注射完全弗氏佐剂 (CFA)建立类风湿关节炎 (RA)的动物模型—AA。用蛋白质印迹 (Westernblot)法研究AA大鼠肺组织中活化NF κB蛋白水平 ,用原位杂交法进一步研究AA大鼠肺组织中NF κBmRNA水平 ,用显微图像分析系统对其表达进行定量分析。结果　在AA大鼠肺组织中可见肺泡变形 ,肺泡毛细血管基底膜损伤 ,间质内可见淋巴细胞、浆细胞及巨噬细胞浸润。AA组活化NF κB蛋白水平明显高于正常组 (P <0 0 1 ) ,NF κBmRNA的表达也明显高于正常组 (P <0 0 1 )。NF κBmRNA主要表达于肺内巨噬细胞、浆细胞以及浸入肺间质内的淋巴细胞中。结论　AA大鼠肺组织的病理改变与RA患者肺组织的病理改变相似 ,且NF κB参与AA肺组织的病理过程     

佐剂性关节炎早期病变的X线位相对比成像研究

目的：应用X线位相对比成像活体研究佐剂性关节炎(AA)大鼠早期的骨关节改变。方法：SD大鼠左后足爪皮下注射弗氏完全佐剂(CFA)建市AA模型后．于病变早期进行连贯的右后足爪X线位相对比成像．观察其骨关节的动态变化．同时进行足爪肿胀度、体重等生理指标的检测和传统X线成像。最后．苏木素-伊红(HE)染色行AA大鼠足爪的病理检查．结果：佐剂性关节炎大鼠有后足爪跖趾关节在致炎后第10天．骨质改变不明显，仅表现为周围软组织肿胀第12天骨性关节面及其下出现骨质破坏、骨质疏松．周围软组织肿胀加重。第14天骨质破坏区扩大、融合．尤其边缘部化表现明显。第16天．骨性关节面及其下骨质破坏区仍然存在．关节间隙与正常间隙比较显示增宽，周围软组织肿胀显著．第18天．可见明确的骨膜新生骨形成，骨质破坏区缩小．关节周围骨质密度增高．软组织肿胀减轻。X线位相对比成像能清楚显示上述改变．而传统X线成像却不能分辨。足爪容积及体重在实验期间出现相应变化．并且与正常组比较差异有显著性。随后的病理检查证实了佐剂性关节炎的存在。结论：佐剂性关节炎早期除显著的周围软组织肿胀、关节间隙增宽外，还可出现骨质疏松、骨质破坏以及骨膜增生．并且呈动态变化过程、X线位相对比成像能清楚地活体显示佐剂性关节炎的细微骨质改变，这是以往任何影像方法都无法比的．因此可以作为一种非常有效的检测手段而广泛应用于相关研究。     

Destructive pneumococcal septic arthritis in end-stage renal disease

Summary Pneumococcal arthritis generally presents as non-destructive monoarthritis, although some underlying metabolic disorders such as liver failure and diabetes have been suggested to represent a risk factor for severe joint disease. Here we report a case of destructive pneumococcal arthritis of the left hip joint in a patient suffering from chronic renal failure treated with hemodialysis for ten years. Inspite of effective anti-pneumococcal antibiotic treatment, the patient with pre-existing renal osteopathy and a mild osteoarthritis continued to suffer from severe and disabling pain of the left hip. This case demonstrates that pneumococcal joint infection in patients with underlying uremic bone disease can lead to quick deterioration of the affected joint.     

A CCR-5 antagonist inhibits the development of adjuvant arthritis in rats

SIR, Chemokine receptor CCR5 is preferentially expressed onTh1 lymphocytes and has been reported to have important rolesin the pathogenesis of rheumatoid arthritis (RA). Yang et al.[1] demonstrated that a CCR5 antagonist inhibits the developmentof arthritis in the collagen-induced arthritis (CIA) model inmice. They showed that the inhibition of the development ofarthritis is not caused by affecting the generation of collagen-sensitizedT cells but by interfering with their migration to joint lesions.     

Primary cultured T cell vaccine for adjuvant arthritis (AA), collagen-induced arthritis (CA) and arthritis in HTLV-1 pX-transgenic mice as models of rheumatoid-like arthritis: dominancy of the roles of T cells or humoral factors in the pathogenesis of CA and pX-transgenic arthritis

Abstract

It has been reported that a T cell vaccine is capable of regulating auto-reactive T cells, and may be used for protection against and treatment of adjuvant arthritis (AA), but no reports have appeared regarding other forms of autoimmune arthritis. In this paper, we aimed for protection against and treatment of collagen-induced arthritis (CA) and arthritis induced in HTLV-1 pX-transgenic mice (pX-A) with a T cell vaccine as another model of autoimmune arthritis, in addition to a parallel study on AA. Drained lymph node lymphocytes were cultured in either Mycobacterium tuberculosis, type II collagen or in an anti-CD3 antibody immobilized dishes for a total of 7 days. These cells were then fixed with 0.5% glutaraldehyde and used as a T cell vaccine. This was applied in the following five groups: protection and treatment of AA, protection (tolerance induction) and treatment of CA, and treatment of pX-a. The effects of a T cell vaccine were examined as: (i) an arthritis score, (ii) a histopathological examination of joint lesions, (iii) serum titers of anti-type II collagen antibodies and (iv) serum levels of several cytokines. In terms of the arthritis score, although the T cell vaccine was effective both in the protection of and treatment against AA, it was not effective for either CA or pX-A. The serum titers of anti-collagen antibodies were unchanged in the four groups examined. The serum levels of interleukin-1 β showed almost no differences in the four groups. Serum levels of tumor necrosis factor-α and interferon-γ were significantly higher in the pX-A treatment group. The T cell vaccine was effective in both protecting against and treating AA; however, it was not effective with regard to CA and pX-A. The possible dominancy of T cells in the pathogenesis of each autoimmune arthritis was discussed.     

Primary cultured T cell vaccine for adjuvant arthritis (AA), collagen-induced arthritis (CA) and arthritis in HTLV-1 pX-transgenic mice as models of rheumatoid-like arthritis: dominancy of the roles of T cells or humoral factors in the pathogenesis of CA and pX-transgenic arthritis

It has been reported that a T cell vaccine is capable of regulating auto-reactive T cells, and may be used for protection against and treatment of adjuvant arthritis (AA), but no reports have appeared regarding other forms of autoimmune arthritis. In this paper, we aimed for protection against and treatment of collagen-induced arthritis (CA) and arthritis induced in HTLV-1 pX-transgenic mice (pX-A) with a T cell vaccine as another model of autoimmune arthritis, in addition to a parallel study on AA. Drained lymph node lymphocytes were cultured in eitherMycobacterium tuberculosis, type II collagen or in an anti-CD3 antibody immobilized dishes for a total of 7 days. These cells were then fixed with 0.5% glutaraldehyde and used as a T cell vaccine. This was applied in the following five groups: protection and treatment of AA, protection (tolerance induction) and treatment of CA, and treatment of pX-a. The effects of a T cell vaccine were examined as: (i) an arthritis score, (ii) a histopathological examination of joint lesions, (iii) serum titers of anti-type II collagen antibodies and (iv) serum levels of several cytokines. In terms of the arthritis score, although the T cell vaccine was effective both in the protection of and treatment against AA, it was not effective for either CA or pX-A. The serum titers of anti-collagen antibodies were unchanged in the four groups examined. The serum levels of interleukin-1 β showed almost no differences in the four groups. Serum levels of tumor necrosis factor-α and interferon-γ were significantly higher in the pX-A treatment group. The T cell vaccine was effective in both protecting against and treating AA; however, it was not effective with regard to CA and pX-A. The possible dominancy of T cells in the pathogenesis of each autoimmune arthritis was discussed.