Cake M A, Read R A, Guillou B, Ghosh P
Division of Veterinary and Biomedical Sciences, Murdoch University, Perth, Western Australia.
Osteoarthritis Cartilage. 2000 Nov;8(6):404-11. doi: 10.1053/joca.1999.0315.
To examine the effect of an oral preparation of avocado and soya unsaponifiables (ASU) on the development of joint pathology in an ovine model of osteoarthritis (OA), using computer-assisted histomorphometric methods.
OA was induced in ovine knee joints by bilateral lateral meniscectomy (N=32). ASU (900 mg/weekday) was given orally to half the group (MenX+ASU), the remainder receiving placebo (MenX). Sixteen animals were used as non-operated controls (NOC). At 3 and 6 months post-meniscectomy, histological sections from the medial and lateral femoral condyles (MFC, LFC), tibial plateaux (MTP, LTP) and trochlear groove (TG) were prepared from all joints. Sections were scored using traditional histopathological scales, and computerized image analysis, measuring total cartilage area, uncalcified cartilage (UCC) and subchondral bone plate (SCP) thickness, and intensity of articular cartilage toluidine blue staining (mean greyscale intensity, black=255) as an index of proteoglycan (PG) content.
Computerized image analysis showed significant histological differences not detectable by traditional scoring methods. ASU-treated animals at 6 months showed reduced loss of toluidine blue stain in the MTP (P=0.015) and LTP (P=0.001), and significantly greater staining in the TG than either placebo or NOC groups (P=0.011). UCC thickness increased after meniscectomy, but tended to be highest in ASU-treated animals, significantly so in the middle zone of the LFC (MenX+ASU: 1.03+/-0.21mm vs MenX: 0.79+/-0.14 mm, P=0.018; NOC: 0.77+/-0.17 mm). Lateral compartment SCP thickness increased post-meniscectomy but was increased significantly less in the inner zone of the LTP in ASU-treated sheep (MenX+ASU: 1.37+/-0. 23 mm vs MenX: 1.68+/-0.28 mm, P=0.033; NOC=1.22+/-0.33 mm).
In this model ASU treatment following meniscectomy appeared to confer a subtle but statistically significant protective effect on articular cartilage. Although the drug failed to prevent focal cartilage lesions, characteristic of this model, histomorphometric analysis demonstrated greater PG content and UCC thickness in adjacent joint regions of ASU-treated animals. In addition, a statistically significant reduction of subchondral bone sclerosis was noted in the LTP region of the drug-treated group. An anabolic effect on chondrocytes, resulting in the stimulation of matrix production in regions distant to the insult, was also suggested by the data. These findings support other studies which have proposed that ASU may exhibit disease-modifying anti-OA activity.
采用计算机辅助组织形态计量学方法,研究口服鳄梨大豆非皂化物(ASU)制剂对骨关节炎(OA)绵羊模型关节病变发展的影响。
通过双侧外侧半月板切除术诱导绵羊膝关节发生OA(N = 32)。该组一半动物口服ASU(900毫克/工作日)(MenX + ASU),其余动物接受安慰剂(MenX)。16只动物作为未手术对照(NOC)。在半月板切除术后3个月和6个月,从所有关节获取内侧和外侧股骨髁(MFC、LFC)、胫骨平台(MTP、LTP)和滑车沟(TG)的组织学切片。使用传统组织病理学量表和计算机图像分析对切片进行评分,测量总软骨面积、未钙化软骨(UCC)和软骨下骨板(SCP)厚度,以及关节软骨甲苯胺蓝染色强度(平均灰度强度,黑色 = 255)作为蛋白聚糖(PG)含量的指标。
计算机图像分析显示出传统评分方法无法检测到的显著组织学差异。在6个月时,接受ASU治疗的动物MTP(P = 0.015)和LTP(P = 0.001)的甲苯胺蓝染色损失减少,且TG中的染色明显高于安慰剂组或NOC组(P = 0.011)。半月板切除术后UCC厚度增加,但在接受ASU治疗的动物中往往最高,在LFC中间区域显著如此(MenX + ASU:1.03±0.21毫米 vs MenX:0.79±0.14毫米,P = 0.018;NOC:0.77±0.17毫米)。外侧间室SCP厚度在半月板切除术后增加,但在接受ASU治疗的绵羊LTP内侧区域增加明显较少(MenX + ASU:1.37±0.23毫米 vs MenX:1.68±0.28毫米,P = 0.033;NOC = 1.22±0.33毫米)。
在该模型中,半月板切除术后ASU治疗似乎对关节软骨具有微妙但具有统计学意义的保护作用。尽管该药物未能预防该模型特有的局灶性软骨损伤,但组织形态计量学分析表明,接受ASU治疗的动物相邻关节区域的PG含量和UCC厚度更高。此外,在药物治疗组的LTP区域,软骨下骨硬化有统计学意义的降低。数据还表明对软骨细胞有合成代谢作用,导致在远离损伤部位的区域刺激基质产生。这些发现支持了其他提出ASU可能具有改善疾病的抗OA活性的研究。