Timosaponin B-II可减轻缺血性卒中后阿尔茨海默病相关病理的出血性转化加速
Timosaponin B-II attenuates hemorrhagic transformation-driven acceleration of alzheimer disease-related pathology after ischemic stroke.
摘要(中文译文)
出血性转化(HT)是缺血性卒中后再灌注治疗的主要并发症，但其对阿尔茨海默病(AD)进展的影响仍不清楚。在本研究中，我们采用早期APP/PS1小鼠模型，发现短暂性大脑中动脉闭塞(tMCAO)后的出血性转化加重了认知功能障碍并促进了AD样病理改变，而知母皂苷B-II(TB-II)治疗可显著减轻上述改变。TB-II有效缓解了tMCAO后出血性转化(tMCAO/HT)诱导的APP/PS1小鼠认知和识别记忆缺陷，并减少了海马Aβ42的生成。在体外实验中，TB-II预处理逆转了氧糖剥夺/复氧(OGD/R)和氯化血红素诱导的N2a/APPswe细胞Aβ42生成增加、凋亡倾向增强，以及线粒体膜电位和细胞活力下降。在机制上，TB-II激活NRF2，NRF2进而间接调控GSK-3β介导的APP磷酸化，并通过结合启动子负向调控BACE1转录，最终抑制淀粉样蛋白生成途径。综上所述，我们的研究结果表明，TB-II可能作为一种潜在的治疗药物，用于对抗缺血-再灌注后出血性转化相关的AD样病理加速进展。
Abstract
Hemorrhagic transformation (HT) is a major complication of reperfusion therapy after ischemic stroke, but its impact on Alzheimer disease (AD) progression remains unclear. In this study, we used an early-stage APP/PS1 mouse model and found that HT following transient middle cerebral artery occlusion(tMCAO) aggravated cognitive impairment and promoted AD-like pathological changes, which were markedly attenuated by Timosaponin B-II (TB-II) treatment. TB-II effectively alleviated HT following tMCAO(tMCAO/HT)-induced cognitive and recognition memory deficits in APP/PS1 mice and reduced hippocampal Aβ42 production. In vitro, TB-II pretreatment reversed oxygen-glucose deprivation/reoxygenation (OGD/R) and hemin-induced increases in Aβ42 production and apoptotic propensity, as well as decreases in mitochondrial membrane potential and cell viability in N2a/APPswe cells. Mechanistically, TB-II activated NRF2, which in turn indirectly modulating GSK-3β-mediated APP phosphorylation and negatively regulated BACE1 transcription through binding promoter binding, ultimately suppressing amyloidogenic processing. Together, our findings suggest that TB-II may serve as a potential therapeutic agent against HT-associated acceleration of AD-like pathology after ischemia-reperfusion.
如何引用
AMA
Yafen Dong, Xuesong Bai, Ye Chen, Jian Wang, Qiaoyan Cui, Liming Fan, et al. Timosaponin B-II attenuates hemorrhagic transformation-driven acceleration of alzheimer disease-related pathology after ischemic stroke.. Biochemistry and biophysics reports. 2026; doi:10.1016/j.bbrep.2026.102654.
APA
Yafen Dong, Xuesong Bai, Ye Chen, Jian Wang, Qiaoyan Cui, Liming Fan, et al (2026). Timosaponin B-II attenuates hemorrhagic transformation-driven acceleration of alzheimer disease-related pathology after ischemic stroke.. Biochemistry and biophysics reports. https://doi.org/10.1016/j.bbrep.2026.102654
GB/T 7714
Yafen Dong, Xuesong Bai, Ye Chen, Jian Wang, Qiaoyan Cui, Liming Fan, et al. Timosaponin B-II attenuates hemorrhagic transformation-driven acceleration of alzheimer disease-related pathology after ischemic stroke.[J]. Biochemistry and biophysics reports, 2026 doi:10.1016/j.bbrep.2026.102654.
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