Liu Jun, He Xiaole, Zhen Ping, Chen Hui, Zhou Shenghu, Tian Qi, Wang Rong, Li Xusheng
Department of Orthopaedics, General Hospital of Lanzhou Command, Lanzhou 730050, China.
Department of Gerontology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2017 Feb 28;42(2):121-127. doi: 10.11817/j.issn.1672-7347.2017.02.001.
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.
观察1型沉默信息调节因子(SIRT1)信号通路对软骨细胞代谢及线粒体氧化应激的影响,探讨SIRT1信号通路及薯蓣皂苷元(Dgn)在骨关节炎(OA)发病机制中的作用。方法:建立C57BL/6小鼠(13.5 - 18.0 g)OA模型。将软骨细胞随机分为4组:OA组、Dgn + OA组、Dgn + Sirtinol + OA组和Sirtinol + OA组。采用蛋白质免疫印迹法检测4组中SIRT1、乙酰化调节转录因子1(Ac - FOXO1)和Bax的表达。观察4组线粒体琥珀酸脱氢酶、细胞色素C氧化酶和超氧化物歧化酶水平的变化。结果:与OA组比较,OA + Dgn组SIRT1蛋白表达增加(P < 0.05),Ac - FOXO1和Bax蛋白表达降低(P < 0.05),SDH和COX表达降低,SOD含量降低(P < 0.05)。与OA + Dgn组比较,OA + Dgn + Sirtinol组和Sirtinol + OA组SIRT1表达增加(P < 0.05),Ac - FOXO1和Bax蛋白表达降低(P < 0.05)。OA组SDH和COX表达降低,SOD含量降低,而OA + Dgn + Sirtinol组和Sirtinol + OA组上述指标均逆转(均P < 0.任5)。结论:SIRT1信号通路与OA及软骨细胞凋亡变化密切相关,其中Dgn可能通过激活SIRT1信号通路抑制软骨细胞凋亡、提高软骨细胞线粒体氧化应激能力,在抗OA中发挥保护作用。