英卡膦酸盐对佐剂关节炎模型大鼠骨与关节的影响

Effects of incadronate on bone and joint in rat with adjuvant arthritis

目的:研究英卡膦酸盐对佐剂关节炎大鼠的关节炎症、肿胀以及结构破坏的影响。方法:35只雌性Lewis大白鼠随机分为5组:正常对照组、模型组和英卡膦酸盐低、中、高剂量组,每组7只。除正常对照组外,其余4组接种佛氏完全佐剂诱发关节炎。英卡膦酸盐3个剂量组自接种之日起,连续42d皮下注射英卡膦酸盐0·01,0·1和1mg·kg-1·d-1,qd。记录关节炎分数,测定后足肿胀程度,并观察大鼠后肢放射学和踝关节组织病理学变化。结果:与模型组比较,英卡膦酸盐剂量依赖性地降低关节炎分数和后足肿胀程度;大鼠后肢放射学和踝关节组织病理学变化显示,英卡膦酸盐减轻踝与足部骨、关节的变形破坏,X线分数和TRAP阳性细胞计数剂量依赖性的降低。结论:英卡膦酸盐对大鼠佐剂关节炎的关节炎症、肿胀以及结构破坏具有抑制作用,提示英卡膦酸盐可作为类风湿性关节炎的辅助预防治疗药物。

Objective：To evaluate the effects of incadronate on the joint inflammation, swelling and bone destruction in rat with adjuvant arthritis （AA）. Methods：Thirty-five female Lewis rats were randomly allocated into 5 groups （7 rats per group）. Except normal control, The other 4 groups （one model control and three incadronate-treated） were given an intradermal injection of heat-killed Mycobacterium butyricum to develop AA. In the three incadronate-treated groups, incadronate was injected daily by a single subcutaneous injection with 0.01, 0.1 and 1 mg·kg^-1.d^-1 respectively for 42 d. The effects of incadronate in AA rats were evaluated according to the arthritis score, hind paw volume, radiological and histological examinations. Results：Contrast with model control, incadronate suppressed the radiological and histopathological changes as well as the joint swelling in AA rat in a dose-dependent manner. The number of TRAP-positive cells （osteoclasts and preosteoclasts/precursors） in bone marrow spaces and granulation tissue in the incadronate-treated groups were also reduced in a dose-dependent manner. Conclusions： Incadronate not only inhibits bone destruction,but also abates joint inflammation and swelling in AA rat. These results suggest that incadronate may be a useful drug for the prophylactic treatment of both bone destruction and joint inflammation in rheumatoid arthritis patients