姜黄素对大鼠膝骨性关节炎模型的影响△

Effect of curcumin on pain and cartilage degeneration of knee osteoarthritis in rat

摘要:

［目的］ 探讨姜黄素对膝骨性关节炎 （knee osteoarthritis, KOA） 疼痛与软骨退变的影响。［方法］ 30 只雄性 SD 大鼠，随机分为 3 组，每组 10 只，假手术组 10 只动物仅切开关节囊，其余 20 只动物切断前交叉韧带离断法建立 KOA 大鼠模型。姜黄素组给予姜黄素 （50 mg/kg） 腹腔注射，假手术组和模型组给予等量生理盐水注射，1 次/d，连续 8 周。建模术后 8 周，评价疼痛反应，行组织学观察与评分，ELESIA 法检测滑液 IL-1β、TNF-α，MCP-1 含量，Western blot 法检测软骨 MMP1、MMP-13、Aggrecan 和 Collagen Ⅱ。［结果］与假手术组相比，模型组的 MWT 和 TWL 均显著降低（P<0.05），而 OARSI 组织学评分显著增加（P<0.05）；与模型组相比，姜黄素组 MWT、TWL 显著升高（P<0.05），OARSI 评分显著降低（P<0.05）。ELE- SIA 检测方面，与假手术组相比，模型组 IL-1β、TNF-α、MCP-1 含量均显著升高（P<0.05）；与模型组相比，姜黄素组 IL-1β、 TNF-α、MCP-1 含量均显著降低（P<0.05）。Western blot 检测方面，与假手术组相比，模型组软骨组织 MMP-1、MMP-13 蛋白显著升高，而 Aggrecan 和 Collagen Ⅱ蛋白显著降低（P<0.05）；与模型组相比，姜黄素组 MMP-1、MMP-13 显著降低，而而 Aggre- can 和 Collagen Ⅱ显著升高（P<0.05）。［结论］姜黄素可以显著减轻 KOA 大鼠膝关节的痛觉过敏和软骨退变，其作用机制可能与减少 IL-1β、TNF-α，MCP-1 的含量及恢复软骨代谢平衡有关。

Abstract:

[Objective] To investigate the effects of curcumin on pain and cartilage degeneration of knee osteoarthritis (KOA) in rat. [Methods] Thirty male Sprague-Dawley rats were randomly divided into 3 groups with 10 rats in each group. Ten animals in the sham group received capsulotomy only, while the remaining 20 rats had anterior cruciate ligament resected to establish the KOA rat model. Ten rats in the curcumin group was given curcumin (50 mg/kg) intraperitoneally, while the other 20 animals in the sham and model groups were given the same amount of normal saline once a day for 8 weeks. Eight weeks after modeling, pain response was evaluated, histological observation and scoring were conducted. In addition, ELESIA assay was used for synovial Il-1 β, TNF-α and McP-1, while Western blot assay was con- ducted for MMP-1, MMP-13, Aggrecan and Collagen II of cartilage. [Results] The model group had significantly lower mechanical with- drawal threshold (MWT) and thermal withdrawal latency (TWL) (P<0.05) , while significantly higher Osteoarthritis Research Society Interna- tional (OARSI) histological score than the sham group (P<0.05) . However, the curcumin group got significantly reversed variation in terms of MWT, TWL and OARSI scores compared with those in the model group (P<0.05) . As results of ELESIA assay, the model group had signifi- cantly higher synovial Il-1 β, TNF-α and MCP-1 than the sham group (P<0.05) , whereas which were significantly reversed in the curcumin group (P<0.05) . In term of Western blot assay, the model group had significant increases in MMP-1 and MMP-13, whereas significant de- creases in aggrecan and collagen II compared with the sham group (P<0.05) . Compared with model group, the curcumin group got signifi- cantly decreased MMP-1 and MMP-13 (P<0.05) , while significantly increased aggrecan and collagen II (P<0.05) . [Conclusion] The cur- cumin does considerably reduce hyperalgesia and cartilage degeneration in the KOA rats, which may be related to reducing IL-1β, TNF-α and McP-1 and restoring the balance of cartilage metabolism.