Osteoarthritis (OA) is a common degenerative joint disease that cause pain and disability in adults. Chondrocyte ferroptosis is found to be involved in OA progression. Sappanone A has been found as an anti-inflammatory and antioxidative agent in several diseases. This study aims to investigate the effects of sappanone A on OA progression and chondrocyte ferroptosis. IL-1β-induced chondrocytes and destabilization of the medial meniscus (DMM)-induced rats were respectively used as the OA model in vitro and in vivo. The effects of sappanone A on inflammation, extracellular matrix (ECM) metabolism, and ferroptosis were determined. Our results showed that in IL-1β-induced chondrocytes, sappanone A suppressed the production of NO, PGE2, TNF-α, IL-6, iNOS, and COX2. Sappanone A also inhibited the expression of MMP3, MMP13, and ADAMTS5, while increasing collagen II expression. Moreover, sappanone A alleviated cytotoxicity and decreased the levels of intracellular ROS, lipid ROS, MDA, and iron, while increasing GSH levels. Additionally, sappanone A increased the protein expression of SLC7A11 and GPX4. Administration of ferroptosis activator reversed the inhibitory effects of sappanone A on IL-1β-induced inflammation and ECM degradation. More importantly, Sappanone A activated the Nrf2 signaling by targeting SIRT1. The inhibition of sappanone A on ferroptosis was greatly eliminated due to the addition of SIRT1 inhibitor. Furthermore, intra-articular injection of sappanone A mitigated cartilage destruction and ferroptosis in DMM-induced OA rats. In conclusion, sappanone A protects against inflammation and ECM degradation in OA via decreasing chondrocyte ferroptosis by activating the SIRT1/Nrf2 signaling. These findings deepen our understanding of chondrocyte ferroptosis in OA and highlight the therapeutic potential of sappanone A for OA.

目的:分析关节镜联合胫骨高位截骨术(HTO)与单髁置换术(UKA)治疗膝关节内侧间室骨关节炎的临床疗效.方法:回顾性分析西安交通大学第一附属医院 2018 年 1 月至 2022 年 1 月收治的121 例膝关节内侧间室骨关节炎患者的临床资料,根据患者治疗方式的不同将其分为HTO组(n= 54)和UKA组(n=67).HTO组接受关节镜联合 HTO 治疗,UKA 组接受 UKA 治疗.比较两组临床疗效和围术期基本情况,统计治疗后两组术后并发症发生率,随访记录术后 6 个月、术后 1 年两组患者膝关节功能情况.结果:UKA组临床疗效及总有效率(91.04%vs 77.78%)明显高于 HTO 组(P＜0.05).UKA组术后下床时间、住院时间[(4.83±1.04)d vs(5.32±1.21)d、(10.76±1.55)d vs(11.34±1.18)d]均低于HTO组(P＜0.05).治疗后,UKA组术后并发症发生率(7.46%vs 20.37%)低于HTO组(P＜0.05).术后6 个月、术后1 年,UKA组膝关节HSS评分[(80.27±5.86)分 vs(76.42±7.89)分、(79.23±6.95)分 vs(75.23±8.77)分]均高于同期HTO组(P＜0.05).结论:UKA治疗膝关节内侧间室骨关节炎具有显著疗效,UKA术后并发症更少,术后恢复情况更好.

Objective:This study was to examine the anti-inflammatory effect of sappanone A on interleukin- (IL-) 1β-stimulated osteoarthritis (OA) chondrocytes.Methods:Chondrocytes were pretreated with sappanone A for 2 h before subsequent IL-1β stimulation. The mRNA expression levels of iNOs, COX-2, aggrecan, and collagen-II were measured with qRT-PCR. The levels of TNF-α, IL-6, IL-8, MMP-3, and MMP-13 were determined by ELISA. The protein levels of iNOs, COX-2, ADAMTS-4, ADAMTS-5, aggrecan, collagen-II, p-p65, p65, IκBα, Nrf2, and HO-1 were assessed by Western blot.Results:Sappanone A inhibited the IL-1β-stimulated production of NO, PGE2, iNOS, COX-2, TNF-α, IL-6, and IL-8 in OA chondrocytes. In addition, sappanone A suppressed the expression of MMP-3, MMP-13, ADAMTS-4, and ADAMTS-5 in IL-1β-stimulated OA chondrocytes. The degradation of ECM components was reversed by sappanone A. Sappanone A prevented NF-κB activation while enhanced Nrf2/HO-1 activation in IL-1β-treated chondrocytes.Conclusion:Sappanone A may be a potent therapeutic agent for OA.

目的 分析全膝关节置换术治疗老年膝关节骨性关节炎的临床效果及影响因素.方法 回顾性分析2016年1月—2021年4月收治的膝关节骨性关节炎98例的临床资料.观察临床疗效,比较手术前后膝关节功能、疼痛情况,同时分析影响膝关节骨性关节炎患者临床疗效的因素.结果 98例老年膝关节骨性关节炎治疗后总优良率为92.86％.与术前比较,98例术后疼痛评分下降,膝关节功能改善(P＜0.05).年龄、病情程度、术后半年内康复训练、术前膝关节功能、术前膝关节疼痛程度为膝关节骨性关节炎患者全膝关节置换术临床疗效的独立危险因素(P＜0.05,P＜0.01).结论 全膝关节置换术治疗膝关节骨性关节炎可有效改善患者疼痛及膝关节功能,临床疗效佳,对上述危险因素进行针对性预防及干预对保证临床效果有重要价值.