鳄梨/大豆不皂化物总提取物对实验性犬骨关节炎结构变化的保护作用：一氧化氮合酶和基质金属蛋白酶-13的抑制作用
Protective effects of total fraction of avocado/soybean unsaponifiables on the structural changes in experimental dog osteoarthritis: inhibition of nitric oxide synthase and matrix metalloproteinase-13.
作者信息
Boileau Christelle, Martel-Pelletier Johanne, Caron Judith, Msika Philippe, Guillou Georges B, Baudouin Caroline, Pelletier Jean-Pierre
机构信息
Osteoarthritis Research Unit, University of Montreal Hospital Centre, Notre-Dame Hospital, Sherbrooke Street East, Montreal, Quebec, Canada.
出版信息
Arthritis Res Ther. 2009;11(2):R41. doi: 10.1186/ar2649. Epub 2009 Mar 16.
INTRODUCTION
The aims of this study were, first, to investigate the in vivo effects of treatment with avocado/soybean unsaponifiables on the development of osteoarthritic structural changes in the anterior cruciate ligament dog model and, second, to explore their mode of action.
METHODS
Osteoarthritis was induced by anterior cruciate ligament transection of the right knee in crossbred dogs. There were two treatment groups (n = 8 dogs/group), in which the animals received either placebo or avocado/soybean unsaponifiables (10 mg/kg per day), which were given orally for the entire duration of the study (8 weeks). We conducted macroscopic and histomorphological analyses of cartilage and subchondral bone of the femoral condyles and/or tibial plateaus. We also conducted immunohistochemical analyses in cartilage for the following antigens: inducible nitric oxide synthase, matrix metalloproteinase (MMP)-1, MMP-13, a disintegrin and metalloproteinase domain with thrombospondin motifs (ADAMTS)4 and ADAMTS5.
RESULTS
The size of macroscopic lesions on the tibial plateaus was decreased (P = 0.04) in dogs treated with the avocado/soybean unsaponifiables. Histologically, in these animals the severity of cartilage lesions on both tibial plateaus and femoral condyles, and the cellular infiltration in synovium were significantly decreased (P = 0.0002 and P = 0.04, respectively). Treatment with avocado/soybean unsaponifiables also reduced loss of subchondral bone volume (P < 0.05) and calcified cartilage thickness (P = 0.01) compared with placebo. Immunohistochemical analysis of cartilage revealed that avocado/soybean unsaponifiables significantly reduced the level of inducible nitric oxide synthase (P < 0.05) and MMP-13 (P = 0.01) in cartilage.
CONCLUSIONS
This study demonstrates that treatment with avocado/soybean unsaponifiables can reduce the development of early osteoarthritic cartilage and subchondral bone lesions in the anterior cruciate ligament dog model of osteoarthritis. This effect appears to be mediated through the inhibition of inducible nitric oxide synthase and MMP-13, which are key mediators of the structural changes that take place in osteoarthritis.
引言
本研究的目的，其一，是研究鳄梨/大豆不皂化物治疗对前交叉韧带犬骨关节炎模型中骨关节炎结构变化发展的体内影响；其二，是探究其作用方式。
方法
通过切断杂种犬右膝前交叉韧带诱导骨关节炎。有两个治疗组（每组n = 8只犬），动物分别接受安慰剂或鳄梨/大豆不皂化物（每天10 mg/kg），在整个研究期间（8周）口服给药。我们对股骨髁和/或胫骨平台的软骨和软骨下骨进行了宏观和组织形态学分析。我们还对软骨中的以下抗原进行了免疫组织化学分析：诱导型一氧化氮合酶、基质金属蛋白酶（MMP）-1、MMP-13、含血小板反应蛋白基序的解聚素和金属蛋白酶结构域（ADAMTS）4和ADAMTS5。
结果
用鳄梨/大豆不皂化物治疗的犬，胫骨平台上宏观病变的大小减小（P = 0.04）。组织学上，在这些动物中，两个胫骨平台和股骨髁上软骨病变的严重程度以及滑膜中的细胞浸润均显著降低（分别为P = 0.0002和P = 0.04）。与安慰剂相比，用鳄梨/大豆不皂化物治疗还减少了软骨下骨体积的损失（P < 0.05）和钙化软骨厚度（P = 0.01）。软骨的免疫组织化学分析显示，鳄梨/大豆不皂化物显著降低了软骨中诱导型一氧化氮合酶的水平（P < 0.05）和MMP-13的水平（P = 0.01）。
结论
本研究表明，用鳄梨/大豆不皂化物治疗可减少骨关节炎前交叉韧带犬模型中早期骨关节炎软骨和软骨下骨病变的发展。这种作用似乎是通过抑制诱导型一氧化氮合酶和MMP-13介导的，它们是骨关节炎中发生结构变化的关键介质。
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