Ⅱ型胶原口腔喷雾剂对小鼠胶原性关节炎的治疗作用(英文)

目的　观察鸡Ⅱ型胶原 (CⅡ )口腔喷雾剂对小鼠胶原性关节炎 (CIA)是否具有治疗作用及相关的机理。方法　建立小鼠CIA模型 ,观测关节积分变化。MTT法检测脾淋巴细胞增殖反应 ,腹腔巨噬细胞产生白介素 1(IL 1)及脾淋巴细胞产生白介素 2 (IL 2 )的活性。结果　CⅡ口腔喷雾剂 (5 ,10 ,2 0μg·kg- 1·d- 1× 10d ,免疫后d 2 5～d 35 )均能降低CIA小鼠关节积分 ,且作用与igCⅡ (10 μg·kg- 1·d- 1× 10d)及泼尼松龙 (2mg·kg- 1·d- 1× 10d)相当。口腔喷雾CⅡ (10 ,2 0 μg·kg- 1·d- 1× 10d)能抑制CIA小鼠刀豆蛋白A诱导的脾淋巴细胞增殖反应和IL 1、IL 2的产生活性。结论　CⅡ口腔喷雾剂能抑制CIA小鼠多发性关节炎 ,提示其对CIA小鼠有治疗作用。其机理可能与改善CIA小鼠异常的免疫功能有关。     

鸡Ⅱ型胶原对小鼠胶原性关节炎的治疗作用

目的　研究鸡Ⅱ型胶原 (CⅡ )对小鼠胶原性关节炎(CIA)的治疗作用。方法　在建立小鼠CIA模型的基础上 ,观测关节积分变化 ,同时检测脾淋巴细胞增殖反应 ,白细胞介素 1(IL 1)和IL 2。结果　CⅡ 5、10、2 0 μg·kg-1ig× 7d能明显减轻CIA小鼠的关节炎症 ;抑制CIA小鼠过高的ConA诱导的脾细胞增殖反应及小鼠腹腔巨噬细胞IL 1的过度产生 ,降低脾细胞IL 2的产生 ;同时病理检查亦发现CⅡ治疗用药可以减轻CIA小鼠的骨膜增生和炎细胞浸润。结论　CⅡ对CIA具有治疗作用 ,其机制与免疫功能调节有关。     

木瓜苷对小鼠胶原性关节炎的预防作用及初步机制

目的　研究木瓜苷 (GCS)预防用药对小鼠胶原性关节炎 (collagen inducedarthritis,CIA)的影响 ,并探讨其初步机制。方法　昆明种小鼠随机分为 6组 :正常对照组、模型组、木瓜苷三个剂量组和青藤碱组 (SIN) ;鸡Ⅱ型胶原免疫小鼠诱导继发性关节炎 ;足爪容积测定法、关节炎评分法和跖曲踝关节疼痛评分法观察关节炎的发生情况 ;观察胸腺指数、脾脏指数变化 ;3 H TdR参入法检测T、B细胞增殖反应 ;IL 1、IL 2活性的检测采用小鼠淋巴细胞增殖法 ;ELISA法检测血清中抗Ⅱ型胶原抗体水平 ;分光光度法测定局部踝关节PGE水平。结果　小鼠免疫后d 2 4 ,足爪出现红肿 ,继发性炎症高峰期在d 36 ,4 0后炎症逐渐减轻。GCS(6 0、12 0、2 4 0mg·kg-1)和SIN(10 0mg·kg-1)ig对CIA小鼠继发性关节炎有明显的抑制作用 ,降低CIA小鼠踝关节中增高的PGE ;CIA小鼠脾脏指数增加 ,而胸腺指数未见明显的改变 ,GCS能降低增加的CIA小鼠脾脏指数 ,对胸腺指数无明显影响 ;GCS(6 0、12 0、2 4 0mg·kg-1)和SIN (10 0mg·kg-1)使CIA小鼠增高的ConA和LPS诱导的T细胞和B细胞增殖反应降低 ;使T细胞和PMΦ分别产生的高水平IL 2和IL 1降至正常范围 ;并降低CIA小鼠血清中升高的抗CⅡ抗体。结论　GCS和SIN具有明显的抗炎作用 ,此作用可能是通过抑制     

雷公藤红素对胶原性关节炎的作用(英文)

目的:研究雷公藤红素(Tri)对胶原性关节炎的作用.方法:足肿测量仪测定足肿变化;酶联免疫吸附法测定血清抗胶原Ⅱ型抗体;皮肤迟发型变态反应水平测定;白细胞介素-2和白细胞介素-1的测定采用[~3H]TdR掺入法.对后足趾—跖关节作病理切片.结果:Tri 15和30 mg·kg~(-1)·d~(-1),发病3天后给药,改善足肿,抑制抗胶原Ⅱ型抗体水平和迟发型变态反应水平;抑制白细胞介素.1和白细胞介素-2产生;病理检查显示Tri明显抑制关节炎大鼠病理改变.结论:Tri对胶原性关节炎有治疗作用.     

小鼠Ⅱ型胶原性关节炎模型的制备

目的　制备Ⅱ型胶原诱发的小鼠关节炎模型。方法　利用Ⅱ型胶原乳剂皮内注射。结果　与对照组比较,Ⅱ型胶原性关节组小鼠的足爪肿胀和关节评分明显增加,并且Ⅱ型胶原诱发的迟发性变态反应呈阳性,血清中也检测出抗Ⅱ型胶原的抗体。结论　Ⅱ型胶原乳剂皮内注射可制备关节炎小鼠模型。     

积雪草苷对小鼠胶原诱导性关节炎的抑制作用

研究积雪草苷(asiaticoside)对小鼠胶原诱导性关节炎(collagen-induced arthritis，CIA)的作用，并初步探讨其作用机制。建立CIA模型，检测小鼠足爪炎症的肿胀度，石蜡切片HE染色对关节组织进行病理检查，MTT法检测脾淋巴细胞增殖反应，Western blotting法检测关节软组织中环氧酶-2(cyclooxygenase-2，COX-2)蛋白的表达，EIA法测定关节软组织中前列腺素E₂(prostaglandin E₂，PGE₂)水平，ELISA法检测血清中炎症因子TNF-α、IL-6的水平。积雪草苷(10，20及40 mg·kg^-1)灌胃给药能剂量依赖性地减轻CIA小鼠的关节炎症状，抑制CIA小鼠C II胶原诱导的淋巴细胞增殖反应，减少CIA小鼠踝关节软组织中高水平的COX-2表达及PGE₂含量，降低血清中炎症因子TNF-α和IL-6的水平；同时病理检查发现，可以改善局部关节炎症状，抑制CIA小鼠滑膜细胞增生，减轻炎性细胞浸润。结果表明，积雪草苷对CIA具有抑制作用，其机制可能与抑制淋巴细胞增殖、减少COX-2表达及促进炎症因子TNF-α、IL-6释放等有关。     

强的松对胶原诱导性关节炎大鼠的疗效及机制

目的探讨强的松对胶原诱导性关节炎大鼠的疗效及机制。方法建立Ⅱ型胶原蛋白诱导的大鼠关节炎模型;造模成功后随机分为3组,模型对照组,雷公藤组,强的松组;评估各组大鼠关节炎指数;酶联免疫吸附试验检测大鼠血清肿瘤坏死因子-α及白介素-1β水平;观察大鼠滑膜病理(包括炎性浸润、巨噬A型细胞增生、纤维组织增生)。结果给药16d后,强的松组AI较模型对照组明显降低,差异有统计学意义(P<0.01),直至治疗结束,且优于雷公藤组(P<0.05);与正常对照组比较,模型对照组,雷公藤多甙组、强的松组血清TNF-α及IL-1β水平明显增高(均P<0.01);与模型对照组比较,雷公藤多甙组,强的松组血清TNF-α及IL-1β水平明显下降(均P<0.01);与模型对照组比较,强的松组滑膜炎性细胞浸润和巨噬A型细胞增生减低(P<0.05)。结论强的松可下调CIA大鼠血清TNF-α及IL-1β水平并抑制滑膜炎性细胞浸润和巨噬A型细胞增生,从而缓解CIA。     

Ⅱ型胶原性关节炎动物模型的研究概况

１９７７年Ｔｒｅｎｔｈａｍ等〔１〕首次建立了由Ⅱ型胶原诱导的大鼠实验性关节炎模型。８０年代至９０年代初期，国外大量重复，并在临床表现、病理组织学和免疫学等多方面对其进行了广泛、深入的观察研究，使模型不断成熟和完善。目前，它作为人类类风湿性关节炎和其他...     

Effect of a monoclonal antibody against interleukin-4 on collagen-induced arthritis in mice

1. The present study was undertaken to investigate the effect of a monoclonal antibody (11B11 mAb) against interleukin-4 (IL-4) on collagen-induced arthritis (CIA) in mice.
2. 11B11 mAb was daily injected intraperitoneally over a period of 10 days, commencing on the day of immunization with type II collagen (CII).
3. The results showed that the anti-IL-4 mAb markedly augmented both the incidence and the severity of CIA. The augmentation of the disease was associated with a significant increase in anti-CII IgG2a antibody production, proliferative responses of lymph node cells to CII and interferon-γ (IFN-γ) secretion from the lymphoid cells. The production of anti-CII IgG1 antibodies the secretion of IL-4 was markedly reduced in the mAb-treated mice.
4. Thus, the neutralization of IL-4 by 11B11 mAb appears to be effective in augmenting CIA.

     

Effect of tripterine on collagen-induced arthritis in rats.

AIM: To study the therapeutic effect of tripterine (Tri) on collagen-induced arthritis (CIA). METHODS: Collagen type II (Col) 1.5 mg was injected intradermally to induce CIA in rats. Hind paw volumes of rats were measured with a water displacement method. The serum anti-collagen antibody was measured by an enzyme-linked immunosorbent assay. Delayed hypersensitivity was reflected by skin response to Col. Interleukin-1 (IL-1) and interleukin-2 (IL-2) activities were evaluated by [3H]TdR uptake. Joint was evaluated histologically. RESULTS: Tri 15 and 30 mg.kg-1.d-1 given i.g. to rats 3 d after the first sign of arthritis reduced inflammatory swelling, suppressed humoral and skin response to Col, inhibited IL-2 and IL-1 production, reduced pathological progression of joint. CONCLUSION: Tri has a therapeutic effect on CIA.     

The effect of etodolac on type II collagen-induced arthritis in mice

Type II collagen-induced arthritis (CIA) and mice was used as a model to evaluate the effect of etodolac on the arthritic and immunological parameters of the experimental disease. In a preventative protocol, a significant reduction was observed in the number of joints progressing to ankylosis. At high doses (16 mg/kg/day) a significant delay in the onset of arthritis was also observed. No significant effect was seen on the progression of the disease when etodolac was administered in established CIA. No consistent variations were observed in the anti-type II collagen response or other immunological parameters of the experimental arthritis.     

Human TNF-alpha gene vaccination prevents collagen-induced arthritis in mice

TNFalpha is a key factor in the pathogenesis of rheumatoid arthritis. To investigate whether heterologous TNFalpha gene vaccination could induce anti-TNFalpha antibodies via cross-reaction and prevent the inflammatory arthritis, we constructed two plasmids by inserting a full-length cDNA of human TNFalpha into a secreted vector (pSecTag-TNFalpha) and a non-secreted vector (pTARGE-TNFalpha), respectively. Administering either plasmid to collagen-induced arthritis (CIA) mice reduced paw swelling and synovium-infiltrating inflammatory cells. This reduction was accompanied by down-regulated TNFalpha in sera and joints. The spleen cells from treated CIA mice displayed decreased IFN-gamma mRNA levels and matrix metalloproteinase-9 bioactivity in comparison with those from CIA control. Furthermore, both spontaneous and collagen-specific proliferation of the lymphocytes was significantly decreased after treatment. Administration of plasmids led to an elicited production of antibodies to both human and mouse TNFalpha. These results suggest that human TNFalpha gene vaccination prevents CIA in mice likely by inducing cross-reactive antibodies against TNFalpha, and that heterologous gene vaccination might provide an effective therapeutic strategy to battle TNFalpha mediated diseases.     

Cigarette smoke condensate extracts augment collagen-induced arthritis in mice

Although cigarette smoking is a solid environmental risk factor for rheumatoid arthritis (RA) as revealed by epidemiological studies, the scientific basis has not been provided. Proinflammatory cytokines produced by synoviocytes are implicated in the pathogenesis of RA. As cigarette smoke condensate (CSC) is able to up-regulate the production of proinflammatory cytokines from human fibroblast-like synoviocytes, we studied the effect of CSC on induction of arthritis in the mouse model of collagen type II-induced arthritis (CIA). When mainstream CSC or sidestream CSC was administered into DBA/1J mice at the time of immunization with collagen and complete Freund adjuvant, CSC dose-dependently augmented the induction and clinical development of arthritis at both young and older mice. Peritoneal injected mainstream CSC one day before immunization also exhibited the augmenting effect, suggesting the systemic effect of CSC. These results support the etiological role of cigarette smoking in RA.     

Chronotherapy targeting cytokine secretion attenuates collagen-induced arthritis in mice

ObjectiveDiurnal variation of symptoms are observed in rheumatoid arthritis, especially in productions of cytokines that show peak concentrations during mid night. In contrast, cytokines of collagen-induced arthritis (CIA) mice increase in daytimes under Mid-light condition. By using chronotherapy, differences in drug efficacies according to administration time of Baricitinib, a wide ranged cytokine blocker, were examined in CIA mice.MethodsCIA mice were administered a dose of 3 mg/kg of Baricitinib once a day at zeitgeber time (ZT) 0 or ZT12 for 21 days. Arthritis scores, histopathology and factors related to joint destruction in sera were examined. Phosphorylation of STAT3 in liver, expressions of cytokines in spleen, and Interleukin (IL)-6 and tumor necrosis factor (TNF)-α in sera were measured.ResultsIn CIA mice, diurnal variations were observed both in expressions of cytokines and phosphorylation of STAT3. Arthritis scores of ZT0/12 group decreased from day3 as compared to untreated mice, and those of ZT0 group significantly decreased as compared to ZT12 group from day12. Pathological findings, immunohistochemistry of cytokines and Receptor activator of nuclear factor kappa-Β ligand (RANKL)/osteoprotegerin ratio in sera well reflected results of arthritis scores. Diurnal variation of STAT3 phosphorylation was suppressed in ZT0 group. At ZT2, expressions of IL-6/Interferon-γ/TNF/granulocyte–macrophage colony-stimulating factor in ZT0 group were significantly decreased as compared to untreated mice, though not in ZT12 group. In ZT0 group, IL-6 and TNF-α in sera were decreased for longer time than that in ZT12 group.ConclusionChronotherapy using Baricitinib targeting cytokine secretions is effective in CIA mice. Clinical applications of chronotherapy can be expected to enhance the drug efficacy.     

Therapeutic effects of glucosides of Cheanomeles speciosa on collagen-induced arthritis in mice

AIM: To investigate the therapeutic effect of the glucosides of Cheanomeles speciosa (GCS) on the collagen-induced arthritis (CIA) in mice. METHODS: Mice were divided randomly into six groups, including normal, CIA, CIA GCS (60, 120, and 240 mg/kg) and CIA glucosides of Tripterygium wilfordii (GTW) groups. CIA model was based on mice. The effect of GCS in CIA mice was measured by paw-swelling, arthritis scores, and histo-pathological assessment of synovium. Indices of thymus and spleens were measured. Thymocytes and splenocytes proliferation, activity of interleukin-1 (IL-1), and interleukin-2 (IL-2) were assayed by MTT and [3H]TdR method. The level of anti-collagen type Ⅱ (CII) antibody in serum and prostaglandin E (PGE) in ankle were assayed by ELISA and ultraviolet spectrophotometer method, respectively. RESULTS: The onset of paw-swelling was on d 24 after injection of emulsion. The peak of secondary inflammation appeared on d 36 and then declined after d 40. GCS and GTW significantly reduced paw-swe