Smith G N, Myers S L, Brandt K D, Mickler E A
Indiana University School of Medicine, Indianapolis 46202-5103, USA.
Arthritis Rheum. 1998 Jun;41(6):976-85. doi: 10.1002/1529-0131(199806)41:6<976::AID-ART4>3.0.CO;2-R.
To determine if intraarticular injections of hyaluronan (HA) protect against the early stages of joint damage in a canine model of osteoarthritis (OA).
OA was induced in adult mongrel dogs by transection of the anterior cruciate ligament of the left knee. One group of dogs (n=7) was treated with 5 weekly injections of HA (MW 1,500,000) into the operated knee beginning 1 day after ligament transection. The control group (n=6) was injected with saline on the same schedule. Twelve weeks after surgery, all dogs were killed, the severity of pathologic changes of OA was graded, and composition of the cartilage and extent of aggregation of proteoglycans (PGs) synthesized in vitro by cartilage slices were determined.
All dogs showed gross morphologic changes typical of OA in the unstable knee. The severity of joint pathology in HA-treated dogs was comparable with that in the saline-injected controls. In OA cartilage from the saline-treated group, the mean uronic acid concentration was 30-60% greater than that in the contralateral knee. In sharp contrast, the uronic acid concentration in OA cartilage from the HA-treated dogs was 10-30% lower than that in cartilage from the contralateral knee (P=0.02 and P=0.03, respectively, for samples from the medial and lateral femoral condyle). The extent of aggregation of PG synthesized in vitro by cartilage from HA-injected animals was similar to that synthesized by cartilage from the saline-injected dogs.
In this canine model of OA, the series of intraarticular injections of HA did not alter development of osteophytosis or fibrillation. However, the PG concentration of cartilage in the OA knee was significantly reduced by this treatment, suggesting that HA therapy might adversely affect the biomechanical properties of the cartilage.
确定在犬骨关节炎（OA）模型中，关节内注射透明质酸（HA）是否能预防关节损伤的早期阶段。
通过切断成年杂种犬左膝前交叉韧带诱导OA。一组犬（n = 7）在韧带切断后1天开始，每周向手术膝关节注射5次HA（分子量1,500,000）。对照组（n = 6）按相同时间表注射生理盐水。术后12周，处死所有犬，对OA的病理变化严重程度进行分级，并测定软骨成分以及软骨切片体外合成的蛋白聚糖（PGs）聚集程度。
所有犬在不稳定膝关节均表现出典型的OA大体形态学变化。HA治疗组犬的关节病理严重程度与注射生理盐水的对照组相当。在生理盐水治疗组的OA软骨中，平均糖醛酸浓度比健侧膝关节高30 - 60%。形成鲜明对比的是，HA治疗组犬的OA软骨中糖醛酸浓度比健侧软骨低10 - 30%（分别来自内侧和外侧股骨髁的样本，P值分别为0.02和0.03）。HA注射动物的软骨体外合成PG的聚集程度与注射生理盐水犬的软骨合成的相似。
在这个犬OA模型中，一系列关节内注射HA并未改变骨赘形成或纤维化的发展。然而，这种治疗使OA膝关节软骨的PG浓度显著降低，提示HA治疗可能对软骨的生物力学特性产生不利影响。
