rhIL-1Ra抑制大鼠颞下颌关节骨关节炎软骨破坏的研究

The effects of recombinant human interleukin-1 receptor antagonist on the cartilage repair in rat temporomandibular joint with osteoarthritis

目的:探讨关节腔内注射重组人IL-1Ra对实验性大鼠颞下颌关节炎软骨关节修复的影响。方法:取SD大鼠24只,用关节腔内注射Ⅱ型胶原酶法建立双侧颞下颌关节骨关节炎模型,1周后,右侧(实验侧)关节腔内一次性注射重组人IL-1Ra5μg(稀释于0.05 ml生理盐水),左侧(对照侧)注射等量生理盐水。建模后2周、4周各处死12只动物,取颞下颌关节标本进行HE染色、免疫组化染色及RT-PCR检测,用Mankin评分方法评估TMJ组织病理变化程度。另取1只SD大鼠用作空白对照,2周后处死。结果:2周时双侧颞下颌关节软骨均呈现不同程度的关节病损,实验侧和对照侧Mankin计分分别为1.33±0.52和2.00±6.63(P>0.05)。4周时,实验侧改良和对照侧Mankin评分分别为3.00±0.63和6.50±0.84(P<0.05),ADAMTS-4、5的蛋白及mRNA表达也低于对照侧(P<0.05)。结论:颞下颌关节腔内注射重组人IL-1Ra能缓解骨关节炎导致的软骨病损,其治疗机制可能是通过抑制ADAMTS-4、5的表达来实现的。

Objective： To investigate the effects of recombinant human interluekin- 1 receptor antogonist （ rhIL- 1Ra） on the cartilage repair in rat temporomandibular joint（TMJ） with osteoarthritis（OA）. Methods： Collagenase-II was injected into bilateral TMJs of 24 adult rats for the induction of bilateral TMJOA, 1 week after injection, 51xg rhIL-1Ra（ diluted in 0.05 ml normal saline） was injected into each right TMJ and the left joint received the same amount of normal saline injection as the control. 12 animals were sacrificed at 2 and 4 weeks after the first injection respectively. HE staining, immunnohistochemical method and RT-PCR examination were conducted. Mankins scere was used to evaluate the TMJOA degree. 1 adult SD rat was used as healthy control, and sacrificed at 2 weeks of the experiment. Results： The TMJs of both sides showed typical OA-related cartilage degradation 2 week after IL-1Ra treatment, the Mankin＇s score of the IL- 1Ra treated and control joints was 1.33± 0.52 and 2.00 ± 6.63 （ P 〉 0.05 ）, 4 week after treatment that was 3.00 ±0.63 and 6.50 ± 0.84（P 〈 0.05）, respectively. Lower expression of ADAMTS-4 and ADAMTS-5 was observed in the treated joints than in the controls （P 〈 0.05 ）. Conclusion： Intra-articular injection of IL-1Ra into TMJ can alleviate the cartilage lesion, the mechanism may lie in the inhibition of the expression of ADAMTS-4 and ADAMTS-5.