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用甘氨酸铜诱导豚鼠侵蚀性关节病及其用抗风湿药物治疗

The induction of an erosive arthropathy in the guinea pig with copper II bisglycinate and its treatment with antirheumatic drugs.

作者信息

Cashin C H

出版信息

Br J Rheumatol. 1987 Aug;26(4):251-8. doi: 10.1093/rheumatology/26.4.251.

Abstract

Single intra-articular injections of copper II bisglycinate [Cu(II)gly] (30-300 micrograms) into guinea-pig knee joints induce progressive joint degradation which first appears after about 2 weeks and peaks about 12 weeks after injection. The stable complex, copper II bishistidinate (300 micrograms) was without effect. The Cu(II)gly induced syndrome has features more in common with osteoarthritis than rheumatoid arthritis in that erosion occurs in the absence of persistent synovial inflammation. The possibility that the damage may be caused by Cu(II)gly inducing free radical formation within the joint, leading to a self-perpetuating chain reaction is discussed. D-Penicillamine and other drugs were tested for their effects on the histological changes induced 4 weeks after the intra-articular injections of 100 micrograms Cu(II)gly. Few significant effects were observed and these were restricted to D-penicillamine, which caused inconsistent protection, sodium aurothiomalate which protected at a dose causing weight loss and prednisolone which exacerbated joint damage. It is concluded that the variability of the control response will need to be reduced before the model can be used for routine drug evaluation but it may be of value in the study of chronic degradative joint disease.

摘要

向豚鼠膝关节内单次注射双甘氨酸铜II [Cu(II)gly](30 - 300微克)会引发渐进性关节退变,这种退变大约在2周后首次出现,并在注射后约12周达到峰值。稳定的配合物双组氨酸铜II(300微克)则没有这种作用。Cu(II)gly诱导的综合征与骨关节炎的共同特征比类风湿关节炎更多,因为在没有持续性滑膜炎症的情况下会发生侵蚀。文中讨论了损伤可能是由Cu(II)gly在关节内诱导自由基形成,从而导致自我延续的连锁反应这一可能性。测试了青霉胺和其他药物对关节内注射100微克Cu(II)gly 4周后诱导的组织学变化的影响。观察到的显著影响很少,且仅限于青霉胺,其保护作用不一致;金硫代苹果酸钠在导致体重减轻的剂量下具有保护作用;泼尼松龙则会加剧关节损伤。得出的结论是,在该模型可用于常规药物评估之前,需要降低对照反应的变异性,但它在慢性退行性关节疾病的研究中可能具有价值。

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