Kobayashi T, Notoya K, Nakamura A, Akimoto K
Pharmacology Research Laboratories I, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 17-85, Jusohonmachi 2-chome, Yodogawa-ku, Osaka, 532-8686, Japan.
Inflamm Res. 2005 Jun;54(6):249-55. doi: 10.1007/s00011-005-1351-z.
The therapeutic effect of glucosamine hydrochloride (GH) and chondroitin sulfate (CS) in combination with fursultiamine, a vitamin B1 derivative, on the development of cartilage lesions was investigated in an animal model of osteoarthritis (OA).
The OA model was created by partial medial meniscectomy of the right knee joint (day 0). The rabbits were placed into three experimental groups: operated (OA) rabbits that received placebo treatment, OA rabbits that received GH (1000 mg/kg) + CS (800 mg/kg), and OA rabbits that received GH + CS + fursultiamine (100 mg/kg). Each treatment was initiated on day 3 and continued for 8 weeks. Macroscopic and histologic analyses were performed on the cartilage. The level of MMP-1 in OA cartilage chondrocytes was evaluated by immunohistochemistry.
Only the group receiving combined treatment with GH + CS + fursultiamine showed a significant reduction in the severity of macroscopic and histologic lesions on tibial plateau, which is the weight bearing cartilage surface of the tibia, compared with placebo-treated OA rabbits. This treatment group also revealed a small, but significant, decrease in the body weight gain of the rabbits. In cartilage from placebo-treated OA rabbits, a significantly higher percentage of chondrocytes in superficial layer stained positive for MMP-1 compared with unoperated control. Rabbits treated with the GH + CS + fursultiamine revealed a significant reduction in the level of MMP-1.
These results suggest that the chondroprotective effect of GH + CS is enhanced by the addition of fursultiamine in experimental OA. This effect was associated with a reduction in the level of MMP-1, which are known to play an important role in the pathophysiology of OA lesions.
在骨关节炎（OA）动物模型中，研究盐酸氨基葡萄糖（GH）、硫酸软骨素（CS）与维生素B1衍生物呋喃硫胺联合使用对软骨损伤发展的治疗效果。
通过右膝关节内侧半月板部分切除术创建OA模型（第0天）。将兔子分为三个实验组：接受安慰剂治疗的手术（OA）兔子、接受GH（1000mg/kg）+CS（800mg/kg）的OA兔子以及接受GH+CS+呋喃硫胺（100mg/kg）的OA兔子。每种治疗在第3天开始，持续8周。对软骨进行宏观和组织学分析。通过免疫组织化学评估OA软骨细胞中MMP-1的水平。
与接受安慰剂治疗的OA兔子相比，仅接受GH+CS+呋喃硫胺联合治疗的组在胫骨平台（胫骨的负重软骨表面）的宏观和组织学损伤严重程度上有显著降低。该治疗组兔子的体重增加也有小幅但显著的下降。在接受安慰剂治疗的OA兔子的软骨中，与未手术对照相比，表层软骨细胞中MMP-1染色阳性的百分比显著更高。接受GH+CS+呋喃硫胺治疗的兔子MMP-1水平显著降低。
这些结果表明，在实验性OA中，添加呋喃硫胺可增强GH+CS的软骨保护作用。这种作用与MMP-1水平的降低有关，已知MMP-1在OA病变的病理生理学中起重要作用。
