Osterman T, Kippo K, Laurén L, Hannuniemi R, Sellman R
Biomedical Research Center, Leiras Oy, Turku, Finland.
Inflamm Res. 1995 Jun;44(6):258-63. doi: 10.1007/BF01782979.
The collagen-induced arthritis model in rats was used to study the effect of disodium clodronate on inflammation and destruction of tarsal, metatarsal, and interphalangeal bones and joints. Female DA rats were immunized with heterologous type II collagen. Fourteen days after immunization, rats with similar scores were assigned to the different experimental groups. They were treated subcutaneously either with saline (controls) or with clodronate at doses of 12.5 and 25 mg/kg/day five times a week for 2 weeks. Clinical signs of arthritis including the severity of paw swelling were assessed weekly. At the time of killing, histological features of the non-decalcified tarsus with tarsal, tarsometatarsal and interphalangeal joints were assessed for inflammatory soft-tissue, articular, and bone changes. All the arthritic control rats developed severe arthritis as shown by the total histological scores of the hindpaw. The treatment with clodronate (25 mg/kg) decreased clinical signs of arthritis, the activity of the collagen-degrading lysosomal enzyme, beta-N-acetylglucosaminidase, in inflamed hindpaw tissue, serum osteocalcin level and serum cross-linked telopeptide of type I collagen level. Histological evaluation indicated moderate arthritis in 29% of the rats and severe arthritis in 71%. The results show that clodronate given therapeutically to arthritic rats, induced with type II collagen, suppresses the intensity of inflammation and bone lesions in the tibiotarsal and tarsometatarsal regions.
采用大鼠胶原诱导性关节炎模型，研究氯膦酸二钠对跗骨、跖骨和指间关节炎症及破坏的影响。雌性DA大鼠用异源性II型胶原免疫。免疫14天后，将得分相似的大鼠分配到不同的实验组。它们每周皮下注射5次生理盐水（对照组）或剂量为12.5和25mg/kg/天的氯膦酸二钠，持续2周。每周评估关节炎的临床症状，包括爪肿胀的严重程度。处死时，评估未脱钙的跗骨以及跗骨、跗跖关节和指间关节的组织学特征，观察炎症软组织、关节和骨骼的变化。所有关节炎对照大鼠均出现严重关节炎，后爪的组织学总评分显示了这一点。氯膦酸二钠（25mg/kg）治疗可减轻关节炎的临床症状，降低炎症后爪组织中胶原降解溶酶体酶β-N-乙酰氨基葡萄糖苷酶的活性、血清骨钙素水平和血清I型胶原交联端肽水平。组织学评估表明，29%的大鼠为中度关节炎，71%为重度关节炎。结果表明，对II型胶原诱导的关节炎大鼠进行治疗性给予氯膦酸二钠，可抑制胫跗关节和跗跖关节区域的炎症强度和骨损伤。
