Haslauer Carla M, Proffen Benedikt L, Johnson Victor M, Hill Adele, Murray Martha M
Department of Orthopaedic Surgery, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115 USA.
Department of Anesthesiology, Boston Children's Hospital, Boston, MA USA.
J Inflamm (Lond). 2014 Nov 1;11(1):34. doi: 10.1186/s12950-014-0034-3. eCollection 2014.
The response of the joint to anterior cruciate ligament (ACL) injury has not been fully characterized. In particular, the characterization of both catabolic factors, including interleukin-6 (IL-6), interleukin-8 (IL-8), and markers of ongoing tissue damage (CRP), and anabolic factors, including vascular endothelial growth factor (VEGF), transforming growth factor β-induced (TGFβI), and the presence of CD163+ macrophages, have not been well defined. In this study, we hypothesized ACL injury would catalyze both catabolic and anabolic processes and that these would have different temporal profiles of expression.
Adolescent Yucatan minipigs were subjected to ACL transection. Within the joint, gene expression levels of IL-6, IL-8, VEGF, and TGFβI were quantified in the synovium, ligament, and provisional scaffold located between the torn ligament ends at days 1, 5, 9, and 14 post-injury. Macrophage infiltration was also assessed in the joint tissues over the two week period. Serum C-reactive protein (CRP) levels were measured at multiple time points between 1 hour to 14 days after injury.
Increases in IL-6 and IL-8 gene expression peaked at day 1 after injury in the synovium and ligament. CRP levels were significantly increased at day 3 before returning to pre-injury levels. VEGF and TGFβI gene expression did not significantly increase until day 9 in the synovium and were unchanged in the other tissues. CD163+ macrophages increased in the ligament and synovium until day 9.
Taken together, these results suggest that the response within the joint is primarily catabolic in the first three days after injury, switching to a more anabolic phase by nine days after injury. The effect of medications which alter these processes may thus depend on the timing of administration after injury.
关节对前交叉韧带（ACL）损伤的反应尚未完全明确。特别是，分解代谢因子，包括白细胞介素-6（IL-6）、白细胞介素-8（IL-8）以及持续组织损伤标志物（CRP），和合成代谢因子，包括血管内皮生长因子（VEGF）、转化生长因子β诱导物（TGFβI）以及CD163+巨噬细胞的存在情况，均未得到很好的界定。在本研究中，我们假设ACL损伤会引发分解代谢和合成代谢过程，且这些过程会有不同的时间表达谱。
对青春期尤卡坦小型猪进行ACL横断。在损伤后第1、5、9和14天，对关节内滑膜、韧带以及位于撕裂韧带两端之间的临时支架中IL-6、IL-8、VEGF和TGFβI的基因表达水平进行定量。在两周时间内还对关节组织中的巨噬细胞浸润情况进行了评估。在损伤后1小时至14天的多个时间点测量血清C反应蛋白（CRP）水平。
IL-6和IL-8基因表达的增加在损伤后第1天在滑膜和韧带中达到峰值。CRP水平在第3天显著升高，之后恢复到损伤前水平。VEGF和TGFβI基因表达直到第9天才在滑膜中显著增加，在其他组织中则无变化。CD163+巨噬细胞在韧带和滑膜中增加，直至第9天。
综上所述，这些结果表明，关节内的反应在损伤后的前三天主要是分解代谢，到损伤后九天转变为更合成代谢的阶段。因此，改变这些过程的药物的效果可能取决于损伤后给药的时间。
