Department of Orthopedics, Yantaishan Hospital, Yantai, Shandong 264001, P.R. China.
Department of Orthopedics, Shandong Jining No. 1 People's Hospital, Jining, Shandong 272011, P.R. China.
Mol Med Rep. 2017 Nov;16(5):6285-6289. doi: 10.3892/mmr.2017.7340. Epub 2017 Aug 23.
The present study aimed to investigate the effect of tanshinone IIA on the degradation of articular cartilage in a rat model of osteoarthritis (OA). The OA rat model was established by anterior cruciate ligament transection (ACLT) and medial meniscus resection (MMx). The animals were treated for 28 days with 0.25‑0.5 mg/kg doses of tanshinone IIA following ACLT + MMx. The knee joints of the rats in the ACLT + MMx group exhibited marked alterations in articular cartilage histopathology and higher Mankin scores, compared with those in the normal group. Tanshinone IIA treatment at a dose of 0.5 mg/kg significantly inhibited cartilage degradation and improved Mankin scores in the OA rat model (P<0.002). Tanshinone IIA treatment completely inhibited the ACLT + MMx‑induced accumulation of inflammatory cells and disintegration of synovial lining in the rats. An increase in the dose of tanshinone IIA between 0.25 and 0.5 mg/kg reduced the proportion of apoptotic chrondrocytes from 41 to 2% on day 29. Treatment of the rats in the ACLT + MMx group with 0.5 mg/kg doses of tanshinone IIA markedly inhibited the expression level of matrix metalloproteinase and increased the expression of tissue inhibitor of metalloproteinase in the rat articular cartilage tissues. Tanshinone IIA treatment significantly reduced the levels of inflammatory cytokines, including interleukin‑1β, tumor necrosis factor‑α and nitric oxide in rat serum samples. The protein expression levels of bone morphogenetic protein and transforming growth factor‑β were significantly increased by tanshinone IIA in the ACLT + MMx rats. Therefore, tanshinone IIA inhibited articular cartilage degradation through inhibition of apoptosis and expression levels of inflammatory cytokines, offering potential for use in the treatment of OA.
本研究旨在探讨丹参酮 IIA 对骨关节炎（OA）大鼠模型中关节软骨降解的影响。OA 大鼠模型通过前交叉韧带切断（ACLT）和内侧半月板切除（MMx）建立。在 ACLT+MMx 后，用 0.25-0.5mg/kg 剂量的丹参酮 IIA 治疗动物 28 天。与正常组相比，ACLT+MMx 组大鼠的膝关节关节软骨组织病理学发生明显改变，Mankin 评分较高。丹参酮 IIA 治疗剂量为 0.5mg/kg 时，可显著抑制 OA 大鼠模型的软骨降解，改善 Mankin 评分（P<0.002）。丹参酮 IIA 治疗完全抑制了 ACLT+MMx 诱导的大鼠炎症细胞积聚和滑膜衬里破坏。在 0.25-0.5mg/kg 剂量范围内增加丹参酮 IIA 的剂量可将第 29 天凋亡软骨细胞的比例从 41%降至 2%。用 0.5mg/kg 剂量的丹参酮 IIA 治疗 ACLT+MMx 组大鼠，明显抑制基质金属蛋白酶的表达水平，增加大鼠关节软骨组织中金属蛋白酶组织抑制剂的表达。丹参酮 IIA 治疗可显著降低大鼠血清中炎症细胞因子（包括白细胞介素-1β、肿瘤坏死因子-α和一氧化氮）的水平。丹参酮 IIA 可显著增加 ACLT+MMx 大鼠中骨形态发生蛋白和转化生长因子-β的蛋白表达水平。因此，丹参酮 IIA 通过抑制细胞凋亡和炎症细胞因子的表达水平，抑制关节软骨降解，为 OA 的治疗提供了潜力。
