Pelletier J, Jovanovic D, Fernandes J C, Manning P, Connor J R, Currie M G, Martel-Pelletier J
Osteoarthritis Research Unit, Louis-Charles Simard Research Center, Centre hospitalier de l'Université de Montréal, Campus Notre-Dame, Montréal, Québec, Canada.
Osteoarthritis Cartilage. 1999 Jul;7(4):416-8. doi: 10.1053/joca.1998.0229.
To evaluate the in-vivo therapeutic efficacy of N -iminoethyl-L-Lysine (L-NIL), a selective inhibitor of inducible nitric oxide synthase (iNOS) in a dose response study, on the progression of lesions in the experimental osteoarthritic (OA) dog model.
The sectioning of the anterior cruciate ligament of the right stifle joint of mongrel dogs was done by a stab wound. Dogs were separated into experimental groups: Group 1 received no treatment, Groups 2, 3, and 4 received oral L-NIL (0.3, 1 or 10mg/kg/day, respectively) starting immediately after surgery. The OA dogs were killed at 12 weeks after surgery.
Macroscopically, L-NIL decreased the size of the cartilage lesions on condyles and plateaus. The histologic severity of the cartilage lesions was decreased in the L-NIL-treated dogs. This effect was more pronounced at the highest dosage tested (3 and 10mg/kg/day).
This study confirms the effectiveness of L-NIL, a selective inhibitor of iNOS, in attenuating the progression of experimental OA. It also clearly shows that the effect is dose-dependent.
在剂量反应研究中，评估诱导型一氧化氮合酶（iNOS）的选择性抑制剂N-亚氨基乙基-L-赖氨酸（L-NIL）对实验性骨关节炎（OA）犬模型中病变进展的体内治疗效果。
通过刺伤对杂种犬右膝关节的前交叉韧带进行切断。将犬分为实验组：第1组不接受治疗，第2、3和4组在手术后立即开始口服L-NIL（分别为0.3、1或10mg/kg/天）。OA犬在手术后12周处死。
宏观上，L-NIL减小了髁和平台上软骨损伤的大小。L-NIL治疗的犬中软骨损伤的组织学严重程度降低。在测试的最高剂量（3和10mg/kg/天）下，这种效果更明显。
本研究证实了iNOS的选择性抑制剂L-NIL在减轻实验性OA进展方面的有效性。它还清楚地表明这种效果是剂量依赖性的。
