文獻DOI：10.1155/2019/2843121
文獻PMID：30944691
文獻原文鏈接：http://doi.org.sci-hub.tw/10.1155/2019/2843121
Role of Combined Lipoic Acid and Vitamin D3 on Astrocytes as a Way to Prevent Brain Ageing by Induced Oxidative Stress and Iron Accumulation
硫辛酸和維生素D3聯(lián)合作用對星形膠質(zhì)細(xì)胞的作用，預(yù)防氧化應(yīng)激和鐵積累誘導(dǎo)導(dǎo)致的腦老化
【Abstract】
Brain ageing is a complex multifactorial process characterized by gradual and continuous loss of neuronal functions. It is hypothesized that at the basis of brain ageing as well as age-related diseases, there is an impairment of the antioxidant defense system leading to an increase of oxidative stress. In this study, two different biological aspects involved in brain ageing and neurodegeneration have been investigated: oxidative stress and iron accumulation damage. In primary mouse astrocytes, the stimulation with 50 μM lipoic acid (LA) and 100 nM vitamin D (vitD) was first investigated in a time-course study to determine the dosages to be used in combination and then in a permeability test using an in vitro blood-brain barrier. In a second set of experiments, the role of oxidative stress was investigated pretreating astrocytes with 200 μM H2O2 for 30 min. The ability of vitD and LA alone and combined together to prevent or repair the damage caused by oxidative stress was investigated after 24h of stimulation by the MTT test, mitochondrial membrane potential measurement, and Western blot analysis. To induce neurodegeneration, cells were pretreated with 300 μM catalytic iron for 6 days and then treated with vitD and LA alone and combined for additional 6 days to investigate the protection exerted by combination, analyzing viability, ROS production, iron concentration, and activation of intracellular pathways. In our study, the combination of LA and vitD showed beneficial effects on viability of astrocytes, since the substances are able to cross the brain barrier. In addition, combined LA and vitD attenuated the H2O2-induced apoptosis through the mitochondrial-mediated pathway. The combination was also able to counteract the adverse conditions caused by iron, preventing its accumulation. All these data support the hypothesis of the synergistic and cooperative activity exerted by LA and vitD in astrocytes indicating a possible new strategy to slow down ageing.
摘要翻譯：
腦老化是一個復(fù)雜的多因素過程共虑，其特征是神經(jīng)元功能的逐漸和持續(xù)喪失戈咳。據(jù)推測，在腦老化以及與年齡相關(guān)的疾病的基礎(chǔ)上扎瓶，抗氧化防御系統(tǒng)受損導(dǎo)致氧化應(yīng)激增加。在這項研究中泌枪，已經(jīng)研究了涉及腦老化和神經(jīng)變性的兩個不同的生物學(xué)方面：氧化應(yīng)激和鐵積累損傷概荷。在原代小鼠星形膠質(zhì)細(xì)胞中，首先在時間過程研究中研究用50μM硫辛酸（LA）和100nM維生素D（vitD）刺激以確定組合使用的劑量碌燕，然后在體外做血腦屏障的滲透性測試误证。在第二組實驗中，研究了氧化應(yīng)激的作用修壕，用200μMH2O2預(yù)處理星形膠質(zhì)細(xì)胞30分鐘愈捅。通過MTT試驗，線粒體膜電位測量和蛋白質(zhì)印跡分析慈鸠，在刺激24小時后研究了單獨的vitD和LA以及組合在一起以預(yù)防或修復(fù)由氧化應(yīng)激引起的損傷的能力蓝谨。為了誘導(dǎo)神經(jīng)變性，將細(xì)胞用300μM催化鐵預(yù)處理6天青团，然后單獨用vitD和LA處理像棘，再合并用6天，研究組合的保護作用壶冒，分析細(xì)胞活力缕题、ROS產(chǎn)生、鐵濃度和細(xì)胞內(nèi)信號活化途徑胖腾。在我們的研究中烟零，LA和vitD的組合顯示出對星形膠質(zhì)細(xì)胞活力的有益影響瘪松，因為這些物質(zhì)能夠穿過腦屏障。此外锨阿，聯(lián)合LA和vitD通過線粒體介導(dǎo)的途徑減弱H2O2誘導(dǎo)的細(xì)胞凋亡宵睦。該組合還能夠抵消由鐵引起的不利條件，防止其積累墅诡。所有這些數(shù)據(jù)都支持LA和vitD在星形膠質(zhì)細(xì)胞中發(fā)揮的協(xié)同和合作活動的假設(shè)壳嚎，這表明可能有一種減緩衰老的新策略。
