Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, China.
Glycoconj J. 2012 Aug;29(5-6):305-13. doi: 10.1007/s10719-012-9407-0. Epub 2012 Jun 12.
Rheumatoid arthritis (RA) is an inflammatory disorder that is characterized by persistent recurrence of joint inflammation leading to cartilage and bone destruction. The present anti-arthritis therapies failed to achieve satisfactory remission in all patients; therefore, it is still necessary to develop novel approaches to fulfill the demand in clinic. Here, we reported the therapeutic effects of lactosyl derivative Gu-4, a synthetic compound that was previously identified as a selective inhibitor against leukocyte integrin CD11b, in a bovine type II collagen induced arthritis (CIA) rat model. First, prophylactic administration of Gu-4 (1.2728 mg/kg) to rats by intraperitoneal injection every 2 days from the first day of collagen immunization significantly decreased the incidence of CIA, diminished the mean paw volume increase, and reduced the number of swollen paws. Second, administration of Gu-4 (1.2728 mg/kg) to rats at early-onset stage of CIA prevented the progression of the pathological process of RA, accelerated the remission of paw edema, and declined the arthritis score; after 5 weeks treatment, X-ray and histological examinations were carried out, the ankle joint of hind limb of Gu-4 treated CIA rats exhibited slighter bone erosion and much less inflammatory cell infiltration compared to those of saline treated animals; furthermore, Gu-4 remarkably attenuated the production of rheumatoid factor (RF) in the serum of CIA rats as determined by ELISA. Moreover, we performed in vitro lymphocyte proliferation assay and found that Gu-4 significantly inhibited the proliferation of splenic lymphocytes isolated from CIA rats in a dose-dependent manner. Our results suggest that Gu-4 can effectively ameliorate CIA and might be an alternative option for the treatment of RA.
类风湿性关节炎（RA）是一种炎症性疾病，其特征为关节炎症持续复发，导致软骨和骨破坏。目前的抗关节炎疗法未能使所有患者达到满意的缓解，因此仍然需要开发新的方法来满足临床需求。在这里，我们报告了乳糖基衍生物 Gu-4 的治疗效果，Gu-4 是一种合成化合物，先前被鉴定为白细胞整合素 CD11b 的选择性抑制剂，在牛型 II 胶原诱导的关节炎（CIA）大鼠模型中。首先，通过腹腔注射，在胶原免疫的第一天开始，每隔 2 天预防性给予大鼠 Gu-4（1.2728 mg/kg），可显著降低 CIA 的发病率，减少平均爪体积增加，并减少肿胀爪子的数量。其次，在 CIA 的早期发病阶段给予 Gu-4（1.2728 mg/kg）可防止 RA 病理过程的进展，加速爪肿胀的缓解，并降低关节炎评分；经过 5 周的治疗后，进行 X 射线和组织学检查，Gu-4 治疗的 CIA 大鼠后肢踝关节的骨侵蚀程度较轻，炎性细胞浸润明显少于盐水处理的动物；此外，Gu-4 显著降低了 CIA 大鼠血清中类风湿因子（RF）的产生，通过 ELISA 测定。此外，我们进行了体外淋巴细胞增殖试验，发现 Gu-4 可显著抑制 CIA 大鼠脾淋巴细胞的增殖，且呈剂量依赖性。我们的结果表明，Gu-4 可有效改善 CIA，可能是治疗 RA 的一种替代选择。
