Altman R D, Dean D D, Muniz O E, Howell D S
Veterans Administration Medical Center, Miami, Florida.
Arthritis Rheum. 1989 Oct;32(10):1300-7. doi: 10.1002/anr.1780321016.
The therapeutic effect of glycosaminoglycan polysulfuric acid ester (GAGPS) was studied using the Pond-Nuki model of canine osteoarthritis. The clinical setting was simulated by permitting 4 weeks ambulation without treatment, following anterior cruciate transection. Animals were then injected with GAGPS, 4 mg/kg intramuscularly, twice weekly during weeks 4-8. Control animals received intramuscular saline. The study was terminated 4 weeks after completion of the GAGPS or saline regimen (i.e., 12 weeks postoperatively). Cartilage from the medial femoral condyle was analyzed for collagen integrity (swelling properties), hydroxyproline, uronic acid, active and total proteoglycan (PG)-degrading metalloproteinase, PG-degrading serine proteinase, and histopathology (Mankin score). Condylar cartilage from animals treated with GAGPS demonstrated less cartilage swelling, less total and active metalloproteinase, and lower histopathologic scores than were found in cartilage from saline-treated animals. GAGPS was able to suppress PG-degrading enzyme activity and maintain a more normal-appearing cartilage. It is proposed that GAGPS suppressed PG breakdown by decreasing synthesis of metalloproteinase or by directly inhibiting metalloproteinase in cartilage, rather than by increasing synthesis of PG by chondrocytes.
采用犬骨关节炎的Pond-Nuki模型研究了硫酸氨基葡聚糖多糖酯（GAGPS）的治疗效果。在前交叉韧带横断后，允许动物在4周内不接受治疗而自由活动，以此模拟临床情况。然后在第4至8周期间，给动物肌肉注射GAGPS，剂量为4mg/kg，每周两次。对照动物接受肌肉注射生理盐水。在完成GAGPS或生理盐水给药方案4周后（即术后12周）终止研究。分析股骨内侧髁软骨的胶原完整性（肿胀特性）、羟脯氨酸、糖醛酸、活性和总蛋白聚糖（PG）降解金属蛋白酶、PG降解丝氨酸蛋白酶以及组织病理学（Mankin评分）。与生理盐水处理动物的软骨相比，接受GAGPS治疗动物的髁软骨表现出更少的软骨肿胀、更少的总金属蛋白酶和活性金属蛋白酶，以及更低的组织病理学评分。GAGPS能够抑制PG降解酶活性，并维持外观更正常的软骨。有人提出，GAGPS通过减少金属蛋白酶的合成或直接抑制软骨中的金属蛋白酶来抑制PG分解，而不是通过增加软骨细胞中PG的合成来实现。
