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J Neuroinflammation:降低血胆固醇不影响实验性自身免疫性脑脊髓炎的神经炎症

2022-02-16 医路坦克 MedSci原创

多发性硬化症(MS)是一种慢性致残的中枢神经系统(CNS)疾病。越来越多的证据表明环境因素在MS的发生、发展过程中起着重要作用,以血脂异常为主要成分的代谢综合征(METS)与MS的不良预后密切相关。

多发性硬化症(MS)是一种慢性致残的中枢神经系统(CNS)疾病,通常影响年轻人。越来越多的证据表明环境因素在MS的发生、发展过程中起着重要作用,以血脂异常为主要成分的代谢综合征(METS)与MS的不良预后密切相关。此外,他汀类降脂药物也被提出用于改善MS的病程。然而,胆固醇也是髓鞘生物发生的限速因子,并促进MS动物模型中的髓鞘再生。因此,疾病期间循环血液胆固醇水平的影响仍然存在争议和争议。 

我们用两种不同的方法评价了循环胆固醇在实验性自身免疫性脑脊髓炎(EAE)疾病MS小鼠模型中的作用:(1)低密度脂蛋白受体(LDLR)缺乏引起的家族性高胆固醇血症小鼠模型;(2)抗PCSK9中和抗体alirocumab的使用,它减少了LDLR的降解,从而降低了血胆固醇水平。

结果:低密度脂蛋白受体缺乏引起的血胆固醇水平升高并未加重EAE小鼠的临床症状。此外,我们观察到抗PCSK9抗体alirocumab不影响EAE的病程,也不调节EAE的免疫应答。

研究表明循环胆固醇不影响EAE疾病的发展。它进一步支持了这样的假设,即他汀类药物的有益作用不能仅仅归因于降低血清胆固醇水平和随之而来的高脂血症的改善,高脂血症被认为是MS的一种共病。然而,这并不排除胆固醇仍然是一个有趣的靶点,应该进一步研究,特别是在中枢神经系统自身免疫的恢复期。

文献来源:Vigne S,  Duc D,  Peter B,et al.Lowering blood cholesterol does not affect neuroinflammation in experimental autoimmune encephalomyelitis.J Neuroinflammation 2022 Feb 07;19(1)

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    2022-04-20 lxg951
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    2023-01-06 xlysu
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    2022-02-22 lujian
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