背景:急性缺血性卒中(AIS)是全球范围内致残和死亡的主要原因。牛膝,一种定期开的传统中草药,由于其具有活血化瘀的能力,在传统中风治疗中起着重要作用。蜕皮甾酮(EDS)是牛膝的关键活性成分之一,具有抗氧化和抗脑缺氧特性。然而,EDS是否能改善AIS,AIS的作用机制尚不清楚。
目的:本研究的目的是观察EDS是否通过ACSL4抑制神经元的铁凋亡来改善AIS引起的氧化损伤。
方法:体内,建立大脑中动脉闭塞(MCAO)大鼠模型进行研究。用EDS治疗后,神经系统评分,TTC,进行HE和FJC染色,其次是氧化应激相关指标的测量,Fe2+的含量,脑组织中铁沉积水平及ACSL4、NCOA4和FTH1的表达。体外,建立氧糖剥夺再灌注(OGD/R)细胞模型。用EDS治疗后,细胞活力,氧化应激相关指标,检测Fe2+含量及ACSL4、NCOA4和FTH1的表达。此外,ACSL4和CETSA技术的过表达进一步阐明了EDS通过ACSL4改善AIS。
结果:结果表明,EDS可以通过抑制铁凋亡来改善MCAO大鼠的氧化损伤,然后提高AIS。重要的是,EDS通过ACSL4抑制铁凋亡,从而抑制MCAO大鼠或OGD/R诱导的PC12细胞的氧化应激。
结论:这些结果提供了证据,证明EDS通过ACSL4抑制铁凋亡改善了AIS引起的氧化损伤,并为EDS作为AIS的有效药物开发候选物的潜在用途提供了新的见解。
BACKGROUND: Acute ischemic stroke (AIS) is a prominent cause of disability and mortality around the world. Achyranthes bidentata Blume, a regularly prescribed traditional Chinese herb, plays a significant role in traditional Chinese stroke therapy due to its ability to promote blood circulation and remove stasis.
Ecdysterone (EDS) is one of the key active components in Achyranthes bidentata Blume, which exhibits antioxidant and anti-cerebral hypoxia properties. However, whether EDS improves AIS and the mechanism of action of AIS is still unclear.
OBJECTIVE: The objective of this study was to observe whether EDS ameliorates oxidative damage caused by AIS by inhibiting ferroptosis in neurons via ACSL4.
METHODS: In vivo, the Middle cerebral artery occlusion (MCAO) rat model was established for research. After treatment with EDS, Neurologic score, TTC, HE and FJC staining were performed, followed by measurements of oxidative stress-related indicators, the content of Fe2+, iron deposition levels and expression of ACSL4, NCOA4 and FTH1 in brain tissue. In vitro, oxygen-glucose deprivation and reperfusion (OGD/R) cell model was established. After treatment with EDS, cell viability, oxidative stress-related indicators, the content of Fe2+ and expression of ACSL4, NCOA4 and FTH1 were detected. In addition, the overexpression of ACSL4 and CETSA technology further elucidated that EDS improves AIS through ACSL4.
RESULTS: The results showed that the treatment of EDS could improve the oxidative damage of MCAO rats by inhibiting ferroptosis, and then improve AIS. Importantly, EDS inhibited ferroptosis via ACSL4, thereby inhibiting oxidative stress in MCAO rats or OGD/R-induced PC12 cells.
CONCLUSIONS: These results provide evidence that EDS ameliorates oxidative damage caused by AIS by inhibiting ferroptosis via ACSL4, and provide new insights into the potential use of EDS as an effective drug development candidate for AIS.