研究动态
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β-谷甾醇的治疗缓解了脑缺血/再灌注损伤的作用,通过抑制胆固醇过载、内质网应激和细胞凋亡。

Treatment with β-sitosterol ameliorates the effects of cerebral ischemia/reperfusion injury by suppressing cholesterol overload, endoplasmic reticulum stress, and apoptosis.

发表日期:2024 Mar
作者: Xiuling Tang, Tao Yan, Saiying Wang, Qingqing Liu, Qi Yang, Yongqiang Zhang, Yujiao Li, Yumei Wu, Shuibing Liu, Yulong Ma, Le Yang
来源: ANTIOXIDANTS & REDOX SIGNALING

摘要:

β-谷甾醇是一种在植物中自然存在的植物固醇。以往的研究已经表明它具有抗氧化、抗高血脂、抗炎、免疫调节和抗肿瘤的作用,但尚不清楚β-谷甾醇治疗是否能减轻缺血性脑卒中的影响。本研究发现,在以大脑中动脉阻塞诱导的小鼠缺血性脑卒中模型中,β-谷甾醇减小了脑梗死和脑水肿的体积,减少了脑组织中神经元凋亡,并改善了神经功能障碍;另外,β-谷甾醇增加了缺氧和葡萄糖耗竭的大脑皮层神经元的活性,并减少了细胞凋亡。进一步研究表明,β-谷甾醇的神经保护作用可能与缺血性脑卒中后细胞内胆固醇积累引起的内质网应激抑制有关。此外,β-谷甾醇与胆固醇的关键转运蛋白NPC1L1表现出较高的亲和力,并对其活性具有对抗作用。总之,β-谷甾醇可能通过抑制神经元细胞内胆固醇超负荷/内质网应激/细胞凋亡信号通路,有助于缓解缺血性脑卒中的治疗。
β-Sitosterol is a type of phytosterol that occurs naturally in plants. Previous studies have shown that it has anti-oxidant, anti-hyperlipidemic, anti-inflammatory, immunomodulatory, and anti-tumor effects, but it is unknown whether β-sitosterol treatment reduces the effects of ischemic stroke. Here we found that, in a mouse model of ischemic stroke induced by middle cerebral artery occlusion, β-sitosterol reduced the volume of cerebral infarction and brain edema, reduced neuronal apoptosis in brain tissue, and alleviated neurological dysfunction; moreover, β-sitosterol increased the activity of oxygen- and glucose-deprived cerebral cortex neurons and reduced apoptosis. Further investigation showed that the neuroprotective effects of β-sitosterol may be related to inhibition of endoplasmic reticulum stress caused by intracellular cholesterol accumulation after ischemic stroke. In addition, β-sitosterol showed high affinity for NPC1L1, a key transporter of cholesterol, and antagonized its activity. In conclusion, β-sitosterol may help treat ischemic stroke by inhibiting neuronal intracellular cholesterol overload/endoplasmic reticulum stress/apoptosis signaling pathways.