Bmi deficiency causes oxidative stress and intervertebral disc degeneration which can be alleviated by antioxidant treatment
Bmi deficiency causes oxidative stress and intervertebral disc degeneration which can be alleviated by antioxidant treatment
复制标题
体重指数缺乏会导致氧化应激和椎间盘退变，可通过抗氧化治疗缓解
DOI：
10.1111/jcmm.15528
复制
发表时间：
2020-06-24
影响因子：
5.3
通讯作者：
Ren, Yongxin
中科院分区：
文献类型：
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作者：
Zhang, Qunhu;Li, Jie;Ren, Yongxin
转录抑制因子Bmi-1参与细胞周期调节和细胞衰老，其缺乏已被证明会引起氧化应激。本研究探讨Bmi-1缺乏是否在椎间盘退变中起促进作用以及抗氧化剂n -乙酰半胱氨酸（NAC）治疗对椎间盘退变的影响。用抗氧化剂NAC （Bmi-1(-/-)+NAC）治疗Bmi-1（-/-）小鼠。在体外实验中，在低氧张力和血清限制条件下，在肿瘤坏死因子α和白细胞介素1 β的存在下培养小鼠椎间盘，以模拟退行性损伤。在这些体外和体内研究中，椎间盘代谢参数通过组织病理学、免疫组织化学和分子方法进行评估。Bmi-1（-/-）小鼠的II型胶原蛋白和聚集蛋白水平较低，胶原蛋白水平较高；与野生型和Bmi-1(-/-)+NAC小鼠相比。Bmi-1（-/-）小鼠超氧化物歧化酶(SOD)-1、SOD-2、谷胱甘肽过氧化物酶(GPX)-1和谷胱甘肽过氧化物酶(GPX)-1和GPX-3水平明显低于野生型和Bmi-1(-/-)+ NAC小鼠。与Bmi-1（-/-）小鼠相比，对照组和Bmi-1(-/-)+NAC小鼠的p16、p21和p53水平明显降低。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中起重要作用。
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 alpha and interleukin 1 beta 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 & x2169; 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.