The transcriptional repressor Bmi‐1 is involved in cell‐cycle regulation and cell senescence, the deficiency of which has been shown to cause oxidative stress. This study investigated whether Bmi‐1 deficiency plays a role in promoting disc degeneration and the effect of treatment with antioxidant N‐acetylcysteine (NAC) on intervertebral disc degeneration. Bmi‐1^−/− mice were treated with the antioxidant NAC, supplied in drinking water (Bmi‐1^−/−+NAC). For in vitro experiments, mouse intervertebral discs were cultured under low oxygen tension and serum‐limiting conditions in the presence of tumour necrosis factor α and interleukin 1β in order to mimic degenerative insult. Disc metabolism parameters in these in vitro and in vivo studies were evaluated by histopathological, immunohistochemical and molecular methods. Bmi‐1^−/− mice showed lower collagen Ⅱ and aggrecan levels and higher collagen Ⅹ levels than wild‐type and Bmi‐1^−/−+NAC mice. Bmi‐1^−/− mice showed significantly lower superoxide dismutase (SOD)‐1, SOD‐2, glutathione peroxidase (GPX)‐1 and GPX‐3 levels than their wild‐type littermates and Bmi‐1^−/−+ NAC mice. Relative to Bmi‐1^−/− mice, the control and Bmi‐1^−/−+NAC mice showed significantly lower p16, p21, and p53 levels. These results demonstrate that Bmi‐1 plays an important role in attenuating intervertebral disc degeneration in mice by inhibiting oxidative stress and cell apoptosis.

中文翻译：

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Bmi缺乏症会引起氧化应激和椎间盘退变，可以通过抗氧化剂治疗来缓解。

转录阻遏物Bmi-1参与细胞周期调节和细胞衰老，已证明其不足会引起氧化应激。这项研究调查了Bmi-1缺乏是否在促进椎间盘退变中起作用以及抗氧化剂N-乙酰半胱氨酸（NAC）治疗对椎间盘退变的影响。Bmi-1 ^-/-小鼠接受了饮用水中提供的抗氧化剂NAC（Bmi-1 ^-/-+ NAC）。在体外实验中，在存在肿瘤坏死因子α和白介素1β的情况下，在低氧张力和血清限制条件下培养小鼠椎间盘，以模拟退化性损伤。通过组织病理学，免疫组织化学和分子方法评估了这些体外和体内研究中的椎间盘代谢参数。与野生型和Bmi-1 ^-/- + NAC小鼠相比，Bmi-1 ^-/-小鼠的Ⅱ型胶原和聚集蛋白聚糖水平较低，而Ⅹ胶原水平较高。与野生型同窝仔和Bmi-1 ^-/- + NAC小鼠相比，Bmi-1 ^-/-小鼠的超氧化物歧化酶（SOD）-1，SOD-2，谷胱甘肽过氧化物酶（GPX）-1和GPX-3的水平明显降低。相对于Bmi-1 ^-/-小鼠，对照组和Bmi-1 ^-/- + NAC小鼠的p16，p21和p53水平显着降低。这些结果表明，Bmi-1通过抑制氧化应激和细胞凋亡在减轻小鼠椎间盘退变方面起着重要作用。