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首页 » 转化医学 » Am J Pathol:新一类抗关节炎药物有效治疗多种炎症性疾病

Am J Pathol:新一类抗关节炎药物有效治疗多种炎症性疾病

来源:生物谷 2014-07-12 13:55

2014年7月12日讯 /生物谷BIOON/--炎症性疾病可以在同一患者不同组织部位同时出现,治疗是复杂的,因为对一种疾病有效的药物可能会加剧其他疾病。其中一个例子就是抗关节炎药物地塞米松,其在减轻了关节炎症疾病同时会加重牙周骨疾病。

发表在The American Journal of Pathology杂志上的一项研究强调了一类新的抗关节炎药物,特别是DTrp8-ɣMSH(DTrp)对多种炎症性疾病的影响,研究提示DTrp通过黑素皮质素(MC)系统作用,可同时减少关节炎症和牙周炎。

MC受体激动剂代表了一类新的能够针对关节炎症疾病的药物,MC受体激动剂在治疗一种炎症疾病的同时不加重对不同器官和组织的不良影响。

60余年前,促肾上腺皮质激素(ACTH)被证明是有效的治疗类风湿和痛风性关节炎药物,但其在临床上的使用是非常零散的。现在,某些促肾上腺皮质激素的抗炎作用通过骨细胞、成纤维细胞和免疫细胞表达的MC受体所介导的。

研究已经表明,促肾上腺皮质激素或其它MC肽活化MC受体可导致对骨损失的多种保护措施,包括增加基质沉积,减少破骨细胞的活化和骨形成细胞增殖的增强。

在这项研究中,研究人员首次确定了诱导实验性关节炎的小鼠是否也表现出牙槽骨的骨质流失。他们发现,骨质流失与小鼠关节的局部炎症严重程度相关。

他们接下来比较选择性地激活小鼠MC3受体的肽与其它已知药物,对关节炎和牙槽骨丧失影响。结果发现虽然糖皮质激素地塞米松发挥强效抗关节炎效果,然而这与防止骨质流失成反比,也即地塞米松会导致骨质流失。

据研究人员Wallace博士表示:利用内源性抗炎机制例如MC系统的药物有许多优点:它们产生了广泛的抗炎作用,促进损伤组织的愈合,并可能与极少数不良影响相关。(生物谷Bioon.com)

 

Association between Periodontal Disease and Inflammatory Arthritis Reveals Modulatory Functions by Melanocortin Receptor Type 3

Trinidad Montero-Melendez, Mila Fernandes Moreira Madeira, Lucy V. Norling, Asil Alsam, Michael A. Curtis, Tarcília Aparecida da Silva, and Mauro Perretti

Because there is clinical evidence for an association between periodontal disease and rheumatoid arthritis, it is important to develop suitable experimental models to explore pathogenic mechanisms and therapeutic opportunities. The K/BxN serum model of inflammatory arthritis was applied using distinct protocols, and modulation of joint disruption afforded by dexamethasone and calcitonin was established in comparison to the melanocortin (MC) receptor agonist DTrp8–γ-melanocyte stimulating hormone (MSH; DTrp). Wild-type and MC receptor type 3 (MC3)-null mice of different ages were also used. There was significant association between severity of joint disease, induced with distinct protocols and volumes of the arthritogenic K/BxN serum, and periodontal bone damage. Therapeutic treatment with 10 μg dexamethasone, 30 ng elcatonin, and 20 μg DTrp per mouse revealed unique and distinctive pharmacological properties, with only DTrp protecting both joint and periodontal tissue. Further analyses in nonarthritic animals revealed higher susceptibility to periodontal bone loss in Mc3r-/- compared with wild-type mice, with significant exacerbation at 14 weeks of age. These data reveal novel protective properties of endogenous MC3 on periodontal status in health and disease and indicate that MC3 activation could lead to the development of a new genus of anti-arthritic bone-sparing therapeutics.

 

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