通过对CD8+T细胞的功能复制和对HBV控制的直接作用,阿斯塔加林抑制B型肝炎病毒
Haohao Li1, Shasha Yang1, Huajun Zhao1
1State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong, China.
European journal of pharmacology
|August 31, 2025
概括
通过减少脂质过氧化,阿斯特拉加林 (AG) 逆转慢性乙型肝炎 (CHB) 中的T细胞耗尽. 这种天然化合物也直接抑制HBV复制,为CHB提供双重治疗方法.
科学领域:
- 免疫学
- 肝病学
- 药理学
背景情况:
- 持续的乙型肝炎病毒 (HBV) 感染会导致肝脏脂质的积累,从而损害免疫功能.
- 慢性HBV (CHB) 患者的细胞毒性T淋巴细胞 (CD8+ T细胞) 显示脂肪过氧化增加,导致T细胞功能障碍.
研究的目的:
- 研究阿斯塔加林 (AG) 对CD8+T细胞功能障碍和HBV复制的影响.
- 阐明AG在慢性HBV感染中的作用机制.
主要方法:
- 在CHB患者中评估脂质过氧化和CD8+T细胞功能.
- 研究了AG对脂质过氧化,氨酸过氧化酶4 (GPX4) 表达和T细胞耗尽的影响.
- 在体内 (小鼠) 和体外 (HepG2. 2. 15细胞) 评估了AG对HBV标志物的作用 (HBsAg,HBVDNA,HBeAg,HBVRNA).
主要成果:
- 通过提高GPX4的调节,AG降低了脂质过氧化和逆转了CD8+ T细胞耗尽.
- 在携带HBV的小鼠中,AG显著降低了血清HBsAg和HBVDNA水平.
- 在细胞中抑制HBsAg,HBeAg和HBVRNA,并诱导抗病毒蛋白MxA的表达.
结论:
- 通过增强CD8+T细胞功能和抑制病毒复制,AG表现出双重抗HBV活性.
- 阿斯特拉加林具有治疗慢性HBV感染的潜力.
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