Protective Effect of SIRT1 Activator on the Knee With Osteoarthritis.
Protective Effect of SIRT1 Activator on the Knee With Osteoarthritis.
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SIRT1激活剂对骨关节炎膝关节的保护作用
DOI：
10.3389/fphys.2021.661852
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发表时间：
2021
影响因子：
4
通讯作者：
Zhu W
中科院分区：
文献类型：
--
作者：
Zhou Z;Deng Z;Liu Y;Zheng Y;Yang S;Lu W;Xiao D;Zhu W
骨关节炎（OA）是最常见的慢性肌肉骨骼疾病之一，被认为与衰老有关。SIRT 1激活剂白藜芦醇是衰老的重要调节剂，可能对OA有潜在的治疗作用。通过内侧半月板失稳手术建立兔OA模型。健康雄性新西兰兔40只，随机分为5组：对照组（假手术）、OA组、低剂量（LD）、中剂量（MD）和高剂量（HD）白藜芦醇治疗OA组。术后6周，对照组和OA组关节腔内注射生理盐水0.8ml，LD组、MD组和HD组关节腔内分别注射5、10和15 μmol/L白藜芦醇0.8ml。给药2周后处死动物，取膝关节软骨行Micro-CT、组织学和Western blot分析。OA组关节软骨损伤明显，关节间隙狭窄。与OA组相比，MD和HD组的骨关节炎改变较少。MD组和HD组的骨体积分数、骨小梁数量和Mankin评分均显著低于LD组和OA组（p < 0.05）。OA组与LD组之间无显著性差异（p > 0.05）。蛋白质印迹法检测SIRT 1和p53的表达与上述结果一致。因此，白藜芦醇可通过激活SIRT 1基因，抑制软骨细胞凋亡、软骨下骨小梁数量增加以及骨密度升高，在OA过程中发挥保护作用。它证明了SIRT 1在维持关节软骨健康方面的重要性，并为OA的治疗提供了有希望的治疗干预。
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 (p < 0.05). No significant difference was found between the OA and LD groups (p > 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.
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影响因子：
11.4
作者：
Jones, Dean P.
通讯作者：
Jones, Dean P.
影响因子：
168.9
作者：
Glyn-Jones, S.;Palmer, A. J. R.;Carr, A. J.
通讯作者：
Carr, A. J.
影响因子：
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作者：
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通讯作者：
Kuroda, Ryosuke
DOI：
10.1038/nrrheum.2016.65
发表时间：
2016-07
期刊：
Nature reviews. Rheumatology
影响因子：
--
作者：
Loeser RF;Collins JA;Diekman BO
通讯作者：
Diekman BO
影响因子：
--
作者：
Gagarina, Viktoria;Gabay, Odile;Dvir-Ginzberg, Mona;Lee, Eun Jin;Brady, Jillian K.;Quon, Michael J.;Hall, David J.
通讯作者：
Hall, David J.