Xia Xinlei, Guo Ji, Lu Feizhou, Jiang Jianyuan
From the Huashan Hospital, Fudan University, Shanghai, People's Republic of China.
Spine (Phila Pa 1976). 2015 May 1;40(9):E515-24. doi: 10.1097/BRS.0000000000000817.
STUDY DESIGN: Experimental animal study of treatment of intervertebral disc (IVD) degeneration. OBJECTIVE: This report aims to evaluate the in vivo effects of SIRT1 on IVD biology and to explore its potential mechanism. SUMMARY OF BACKGROUND DATA: Silent mating type information regulator 2 homolog 1 (SIRT1) has attracted immense attention because of its functions in a variety of aging-related diseases. Despite previous studies indicated that SIRT1 showed a unique expression with degeneration in some in vitro study, there is no in vivo research on the role SIRT1 plays in IVD and its mechanism. METHODS: Coccygeal discs were punctured to induce disc degeneration. Sixteen C57BL/6J mice received either Carboxy methocel (Vehicle) or Resveratrol (RES) gavage. Eight SIRT1 mice and their SIRT1 littermates were also used in this study. At 2 and 6 weeks after puncture, magnetic resonance images were obtained. The mice were subsequently killed, and the spine was extracted for further evaluation. RESULTS: Coccygeal disc puncture caused IVD degeneration in the mice. A SIRT1 activator, RES, markedly ameliorated this pathological change, as demonstrated by stronger signal intensity in the T2-weighted images, as well as a significantly lower magnetic resonance imaging grade (at 2 wk vs. Vehicle group P < 0.001). Histological analysis also revealed an improvement in the RES group compared with the Vehicle group (P < 0.05). Genetic ablation of 1 allele significantly enhanced the level of damage relative to the wild-type mice. In addition, SIRT1 activation suppressed the expression of p16 and at the same time, promoted proliferating cell nuclear antigen and type II collagen expression in disc cells, whereas genetic ablation of 1 allele SIRT1 exhibited the opposite consequence. CONCLUSION: The SIRT1 activator RES protects against puncture-induced disc injury whereas SIRT1 deficiency aggravates tissue injury; the protective role of SIRT1 is partly mediated by suppressing p16, which plays a role in elevating the decreased proliferative ability of the senescent nucleus pulposus cells. LEVEL OF EVIDENCE: N/A.
研究设计：椎间盘退变治疗的实验动物研究。 目的：本报告旨在评估沉默信息调节因子2同源物1（SIRT1）在体内对椎间盘生物学特性的影响，并探讨其潜在机制。 背景资料总结：沉默信息调节因子2同源物1（SIRT1）因其在多种与衰老相关疾病中的作用而备受关注。尽管先前的研究表明，在一些体外研究中SIRT1的表达随退变呈现独特性，但尚无关于SIRT1在椎间盘退变中作用及其机制的体内研究。 方法：穿刺尾椎椎间盘诱导椎间盘退变。16只C57BL/6J小鼠接受羧甲基纤维素（赋形剂）或白藜芦醇（RES）灌胃。8只SIRT1基因敲除小鼠及其同窝野生型小鼠也用于本研究。穿刺后2周和6周时，获取磁共振图像。随后处死小鼠，取出脊柱进行进一步评估。 结果：尾椎椎间盘穿刺导致小鼠椎间盘退变。SIRT1激活剂RES显著改善了这种病理变化，T2加权图像上信号强度增强以及磁共振成像分级显著降低（2周时与赋形剂组相比，P<0.001）即可证明。组织学分析也显示RES组与赋形剂组相比有所改善（P<0.05）。相对于野生型小鼠，1个等位基因的基因敲除显著增强了损伤程度。此外，SIRT1激活抑制了p16的表达，同时促进了椎间盘细胞中增殖细胞核抗原和II型胶原蛋白的表达，而1个等位基因SIRT1的基因敲除则产生相反的结果。 结论：SIRT1激活剂RES可预防穿刺诱导的椎间盘损伤，而SIRT1缺乏则加重组织损伤；SIRT1的保护作用部分是通过抑制p16介导的，p16在提高衰老髓核细胞降低的增殖能力中发挥作用。 证据水平：无。
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