To observe the effect of sirtuin type 1 (SIRT1) signaling pathway on chondrocyte metabolism and mitochondrial oxidative stress, to explore roles of SIRT1 signaling pathway and diosgenin (Dgn) in pathogenesis of osteoarthritis (OA). Methods: To establish C57BL/6 mouse (13.5-18.0 g) model of OA. The chondrocytes were randomly assigned into 4 groups: an OA group, a Dgn+OA group, a Dgn+Sirtinol+OA group, and a Sirtinol+OA group. Expressions of SIRT1, acetylation-regulated transcription factor 1 (Ac-FOXO1), and Bax were detected in the 4 groups by Western blot. Changes in levels of succinate dehydrogenase, cytochrome C oxidase, and superoxide dismutase of mitochondrion in the 4 groups were observed. Results: Compared with the OA group, SIRT1 protein expression was increased in the OA+Dgn group (P<0.05), while the Ac-FOXO1 and Bax protein expressions were decreased (P<0.05), the SDH and COX expressions were decreased, and the SOD content was decreased (P<0.05). Compared with the OA+Dgn group, the SIRT1 expression in the OA+Dgn+Sirtinol group and the Sirtinol+OA group was increased (P<0.05), while the Ac-FOXO1 and Bax protein expressions were decreased (P<0.05). The SDH and COX expressions were decreased, the SOD content was decreased, the SDH and COX expressions were increased, and the SOD content was increased in the OA group (All P<0.05), while those indexes were reversed in the OA+Dgn+Sirtinol group and the Sirtinol+OA group (All P<0.05). Conclusion: The SIRT1 signaling pathway and OA are closely related to changes in chondrocyte apoptosis, in which Dgn may play a protective role in anti-OA by activating SIRT1 signaling pathway to inhibit apoptosis of chondrocytes and to increase chondrocyte mitochondrial oxidative stress capacity.
目的：在小鼠骨性关节炎(osteoarthritis，OA)模型中观察沉默信息转录调控因子1(sirtuin type 1，SIRT1)信号通路对软骨细胞代谢的影响以及线粒体抗氧化应激能力的改变，探讨SIRT1信号通路及薯蓣皂苷元(diosgenin，Dgn)在OA过程中的作用。方法：选择10只C57BL/6小鼠(13.5~18.0 g)建立OA模型，4周后取材，培养软骨细胞并随机分为4组：OA组、 Dgn+OA组、Dgn+Sirtinol(SIRT1通路阻断剂)+OA组及Sirtinol+OA组。运用Western印迹法检测各组细胞SIRT1，乙酰化-调节叉头转录因子1(acetylation-regulated transcription factor 1，Ac-FOXO1)和Bax蛋白的表达，同时检测各组线粒体氧化应激指标琥珀酸脱氢酶(succinate dehydrogenase，SDH)、细胞色素C氧化酶(cytochrome C oxidase，COX)、超氧化物歧化酶(superoxide dismutase，SOD)水平的改变。结果：与OA组比较，Dgn明显增高SIRT1表达水平(P<0.05)，降低Ac-FOXO1和Bax蛋白表达水平(P<0.05)，SDH和COX蛋白表达水平及SOD含量均升高(P<0.05)；而与OA+Dgn组相比，Sirtinol明显降低SIRT1的表达，增高Ac-FOXO1蛋白和Bax蛋白表达水平，降低SDH和COX蛋白表达水平及SOD含量(P<0.05)。结论：SIRT1信号通路和OA中软骨细胞变化密切相关，Dgn通过激活SIRT1通路，有效减轻OA病理过程中软骨细胞的线粒体氧化应激损伤，从而发挥抗OA中软骨细胞保护作用。.