Zhou Zhenquan, Deng Zhenhan, Liu Yuwei, Zheng Yizi, Yang Shiwei, Lu Wei, Xiao Deming, Zhu Weimin
Department of Sports Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, China.
Department of Orthopaedics, Shenzhen Hospital of Southern Medical University, Shenzhen, China.
Front Physiol. 2021 Apr 13;12:661852. doi: 10.3389/fphys.2021.661852. eCollection 2021.
Osteoarthritis (OA), one of the most common chronic musculoskeletal disorders, is deemed to be correlated with aging. The SIRT1 activator, resveratrol, acts as a crucial regulator of aging and may have a potential therapeutic effect on OA. Rabbit OA models were established through destabilized medial meniscus surgery. A total of 40 healthy male New Zealand rabbits were divided into five groups: control group (sham operation), OA group, as well as low dose (LD), middle dose (MD), and high dose (HD) resveratrol-treated OA groups. 6 weeks after operation, 0.8 ml of normal saline was injected into the knee joints every other day in the control and OA groups, and 0.8 ml of 5, 10, and 15 μmol/L resveratrol was injected into the knee joints every other day in the LD, MD, and HD group, respectively. The rabbits were sacrificed 2 weeks after medication, and the articular cartilage of the knee joint was collected for Micro-CT, histology and Western blot analysis. Obvious articular cartilage lesion and joint space narrowing were detected in the OA group. Compared with the OA group, less osteoarthritic changes were observed in the MD and HD groups. The MD and HD groups had significantly lower bone volume fraction, trabecular number and Mankin scores than the LD and OA groups ( < 0.05). No significant difference was found between the OA and LD groups ( > 0.05). The expressions of SIRT1 and p53 detected by western blot were consistent with the aforementioned findings. Therefore, resveratrol can activate the SIRT1 gene to play a protective role in the OA process by inhibiting chondrocyte apoptosis, trabecular bone number increasing of the subchondral bone, as well as elevation of bone density. It demonstrated the importance of SIRT1 in maintaining articular cartilage health and provided a promising therapeutic intervention in the treatment of OA.
骨关节炎（OA）是最常见的慢性肌肉骨骼疾病之一，被认为与衰老相关。SIRT1激活剂白藜芦醇是衰老的关键调节因子，可能对OA具有潜在治疗作用。通过内侧半月板失稳手术建立兔OA模型。将40只健康雄性新西兰兔分为五组：对照组（假手术）、OA组以及低剂量（LD）、中剂量（MD）和高剂量（HD）白藜芦醇治疗的OA组。术后6周，对照组和OA组每隔一天向膝关节注射0.8 ml生理盐水，LD、MD和HD组分别每隔一天向膝关节注射0.8 ml 5、10和15 μmol/L白藜芦醇。给药2周后处死兔子，收集膝关节的关节软骨进行显微CT、组织学和蛋白质印迹分析。OA组检测到明显的关节软骨损伤和关节间隙变窄。与OA组相比，MD组和HD组观察到的骨关节炎变化较少。MD组和HD组的骨体积分数、小梁数量和Mankin评分显著低于LD组和OA组（<0.05）。OA组和LD组之间未发现显著差异（>0.05）。蛋白质印迹检测的SIRT1和p53表达与上述结果一致。因此，白藜芦醇可激活SIRT1基因，通过抑制软骨细胞凋亡、增加软骨下骨小梁数量以及提高骨密度，在OA进程中发挥保护作用。这证明了SIRT1在维持关节软骨健康方面的重要性，并为OA治疗提供了一种有前景的治疗干预措施。
