■临床前动物实验。
■在这项研究中,我们研究了水飞蓟宾在脊髓损伤(SCI)模型中的治疗效果.在SCI中,由于继发性损伤机制引起的细胞损失超过了由原发性损伤引起的细胞损失。Ferroptosis,铁依赖性非凋亡性细胞死亡,已证明对SCI的发病机制有影响。
使用总共78只成年雄性/雌性SpragueDawley大鼠作为体内实验进行研究。组如下:Sham,SCI,去铁胺(DFO)治疗,和水飞蓟宾治疗。有随访时间为24小时的亚组,72小时,6周所有组。丙二醛(MDA),谷胱甘肽(GSH),和Fe2+水平通过分光光度法测量。谷胱甘肽过氧化物酶-4(GPX4),铁电(FPN),转铁蛋白受体(TfR1),和4-羟基壬烯醛(4-HNE)修饰的蛋白质水平通过蛋白质印迹法评估。使用Basso-Beattie-Bresnahan试验评估功能恢复。
■水飞蓟宾在72小时和6周组与SCI相比均实现了MDA和4-HNE水平的显着抑制(p<0.05)。GSH,发现GPX4和FNP水平在水飞蓟宾24小时内显着较高,72小时,6周组与相应SCI组比较(p<0.05)。在72h和6周组的水飞蓟宾处理的大鼠中观察到铁水平的显著降低(p<0.05)。水飞蓟宾在24h和72h组中显著抑制TfR1水平(p<0.05)。观察到恢复能力之间的显著差异如下:水飞蓟宾>DFO>SCI(p<0.05)。
■水飞蓟宾对铁代谢和脂质过氧化的影响,这两者都是铁中毒的特征,可能有助于治疗活动。在此背景下,我们的研究结果认为水飞蓟宾是SCI模型中具有抗生育特性的潜在治疗候选药物.能够有效且安全地减轻铁细胞死亡的治疗剂具有成为未来临床研究的关键点的潜力。
UNASSIGNED: Pre-clinical animal experiment.
UNASSIGNED: In this study, we investigated therapeutic effects of silibinin in a spinal cord injury (SCI) model. In SCI, loss of cells due to secondary damage mechanisms exceeds that caused by primary damage. Ferroptosis, which is iron-dependent non-apoptotic cell death, is shown to be influential in the pathogenesis of SCI.
UNASSIGNED: The study was conducted as an in vivo experiment using a total of 78 adult male/female Sprague Dawley rats. Groups were as follows: Sham, SCI, deferoxamine (DFO) treatment, and silibinin treatment. There were subgroups with follow-up periods of 24 h, 72 h, and 6 weeks in all groups. Malondialdehyde (MDA), glutathione (GSH), and Fe2+ levels were measured by spectrophotometry. Glutathione peroxidase-4 (GPX4), ferroportin (FPN), transferrin receptor (TfR1), and 4-hydroxynonenal (4-HNE)-modified protein levels were assessed by Western blotting. Functional recovery was assessed using Basso-Beattie-Bresnahan test.
UNASSIGNED: Silibinin achieved significant suppression in MDA and 4-HNE levels compared to the SCI both in 72-h and 6 weeks group (p < 0.05). GSH, GPX4, and FNP levels were found to be significantly higher in the silibinin 24 h, 72 h, and 6 weeks group compared to corresponding SCI groups (p < 0.05). Significant reduction in iron levels was observed in silibinin treated rats in 72 h and 6 weeks group (p < 0.05). Silibinin substantially suppressed TfR1 levels in 24 h and 72 h groups (p < 0.05). Significant difference among recovery capacities was observed as follows: Silibinin > DFO > SCI (p < 0.05).
UNASSIGNED: Impact of silibinin on iron metabolism and lipid peroxidation, both of which are features of ferroptosis, may contribute to therapeutic activity. Within this context, our findings posit silibinin as a potential therapeutic candidate possessing antiferroptotic properties in SCI model. Therapeutic agents capable of effectively and safely mitigating ferroptotic cell death hold the potential to be critical points of future clinical investigations.