新型制剂FNS007对Ⅱ型胶原诱导的关节炎大鼠炎症反应和骨损伤的影响

A novel immunosuppressant FNS007 protects against inflammation and bone damage in murine with collagen-induced arthritis

为探讨新型制剂FNS007(又称NTAP)对Ⅱ型胶原(collagen typeⅡ,CⅡ)诱导的关节炎(collagen-induced arthritis,CIA)大鼠炎症反应及骨损伤的作用及其机制,采用Ⅱ型胶原诱导建立CIA大鼠模型。发病大鼠随机分为模型组、FNS007低中高剂量组及阳性药组(甲氨蝶呤组,每周给药2次),另设空白组,隔天一次尾静脉注射给药。观察各组大鼠一般情况及四爪肿胀程度;评价大鼠四爪的炎症评分;治疗结束后X光分析FNS007对CIA大鼠后爪骨损伤的疗效;显微计算机断层扫描技术(micro-computed tomography,micro-CT)扫描大鼠后爪并进行三维重建,观察骨微结构变化并分析后爪跟骨骨小梁厚度等相关参数。结果显示,大鼠在致炎后第14天开始出现关节炎症状;与模型组比较,FNS007治疗后CIA大鼠炎症评分较模型组明显降低;大鼠的X光和CT评分明显降低,骨表面积与骨体积比(BS/BV)明显降低,组织矿物质密度及骨小梁厚度(Tb.Th)明显升高。由此,FNS007对CⅡ诱导的大鼠关节炎炎症症状有明显的抑制作用,对组织损伤和骨破坏有明显的改善作用。以上结果提示FNS007对大鼠CIA有显著的治疗效果,并且具有剂量依赖关系。

To study the effect of FNS007 on inflammation and structural joint and bone damage in a rat model of collagen-induced arthritis（CIA） and its possible mechanism, the rat models were made by intradermal injecting bovine type-Ⅱ collagen with incomplete Freund＇s adjuvant at the base of the tail. At the clinical onset of CIA, rats were randomly divided into six groups according to treatment modality; normal control （control） group, model group, methotrexate （MTX） group, FNS007 low dose group, middle dose group and high dose group. Then each FNS007 group was given the corresponding medicine on the onset of CIA and every other day until the study was terminated. The arthritic score was recorded every other day. On day 22 after injection of the drug, hind paws were removed for analysis of bone morphology by X-ray imaging and micro-computer tomography （micro-CT）, Bone surface area to volume ratio of hone（BS/BV）, tissue mineral density（TMD）and trabeeular thickness（Tb. Th）were determined by analyzing the hind paw calcaneus of CIA rats using micro-CT. FNS007 significantly reduced the arthritic score and inhibited the development of inflammation. X-ray examination and micro-CT analysis demonstrated FNS007 ameliorated bone and joint destruction. Micro-CT data showed that Tb. Th and TMD in model group were significantly lower than those in control group,while BS/BV were significantly higher than those in control group. Compared with model group, Tb. Th and TMD were increased, while BS/BV was significantly decreased in FNS007 groups. FNS007 can inhibit the progression of disease in CIA rats, with reductions in inflammation and bone and joint destruction in a dose-dependent manner.