Ma Yanhong, Yan Xiaoyan, Zhao Huakun, Wang Wei
Department of Rehabilitation Medicine, the Affiliated Sixth People’s Hospital of Shanghai Jiaotong University, Shanghai, China.
Orthopedics. 2012 Aug 1;35(8):e1238-44. doi: 10.3928/01477447-20120725-26.
Based on previous studies showing that interleukin-1 (IL-1) significantly increased after stress shielding, this article reports further research into the possible therapeutic applications of IL-1 receptor antagonist (IL-1Ra). Forty rats whose left Achilles tendons were denervated and completely stress shielded were divided into 5 groups: 2-week phosphate-buffered saline (PBS); 4-week PBS; 2-week IL-1Ra; 4-week IL-1Ra; and normal control. The Achilles tendons were tested morphologically, and the changes in collagen I and III, matrix metalloproteinases (MMP)-1 and -3, and tissue inhibitors of metalloproteinase (TIMP)-1 were determined. The collagen fibrils in the IL-1Ra groups were morphologically more similar to those in the control group than to those in the PBS groups. The collagen I levels increased in the 2-week groups. Significant differences existed between the PBS and IL-1Ra groups at 4 weeks. The MMP-1 level increased dramatically after stress shielding and increased less in the 2-week IL-1Ra group than in the 2-week PBS group. The degree of decrease of MMP-3 in the IL-1Ra groups was significantly less than that in the PBS groups. The collagen III and TIMP-1 levels continued to increase, and no difference was found between the PBS and IL-1Ra groups. Interleukin-1 receptor antagonist prevented morphological deterioration and collagen metabolism of the denervated Achilles tendons after stress shielding, likely by inhibiting the decline of MMP-3 and increasing MMP-1 levels at an early stage.
基于先前研究表明应激屏蔽后白细胞介素-1（IL-1）显著增加，本文报告了对IL-1受体拮抗剂（IL-1Ra）可能的治疗应用的进一步研究。将40只左跟腱去神经支配并完全应激屏蔽的大鼠分为5组：2周磷酸盐缓冲盐水（PBS）组；4周PBS组；2周IL-1Ra组；4周IL-1Ra组；以及正常对照组。对跟腱进行形态学检测，并测定I型和III型胶原蛋白、基质金属蛋白酶（MMP）-1和-3以及金属蛋白酶组织抑制剂（TIMP）-1的变化。与PBS组相比，IL-1Ra组的胶原纤维在形态上与对照组更相似。2周组的I型胶原蛋白水平升高。4周时PBS组和IL-1Ra组之间存在显著差异。应激屏蔽后MMP-1水平显著升高，2周IL-1Ra组的升高幅度小于2周PBS组。IL-1Ra组中MMP-3的降低程度明显小于PBS组。III型胶原蛋白和TIMP-1水平持续升高，PBS组和IL-1Ra组之间未发现差异。IL-1受体拮抗剂可能通过在早期抑制MMP-3的下降并提高MMP-1水平，防止应激屏蔽后去神经支配跟腱的形态恶化和胶原代谢。
