孤儿药物UTTROSIDE B在实验模型中阻碍了MASH的进展和HCC的发展
Tennyson P Rayginia1,2,3, Chenicheri K Keerthana1,2, Sreekumar U Aiswarya1,4,5
1Division of Cancer Research, BRIC-Rajiv Gandhi Centre for Biotechnology (BRIC-RGCB), Thiruvananthapuram 695014, Kerala, India.
JHEP reports : innovation in hepatology
|February 2, 2026
概括
乌特胺B (Utt-B) 有效治疗与代谢功能障碍相关的脂肪肝炎 (MASH),并预防其进展为肝癌. 这种植物素显示为MASH和MASH诱导的肝细胞癌 (HCC) 的新疗法.
科学领域:
- 肝病学和胃肠道学
- 药理学和药物发现
- 在瘤学瘤学.
背景情况:
- 代谢功能障碍相关的脂肪肝炎 (MASH) 是一种严重的肝脏疾病,其特点是脂肪积累,炎症和损伤,可能导致纤维化,肝硬化和肝细胞癌 (HCC).
- 目前对MASH的治疗选择有限,迫切需要有效的治疗方法.
- 乌特化物B (Utt-B) 是一种具有已知的抗HCC特性和FDA孤儿药物指定的植物素,正在研究其对MASH的潜力.
研究的目的:
- 研究Uttroside B (Utt-B) 对改善MASH和预防MASH诱导的肝细胞癌 (HCC) 的疗效.
- 在MASH模型中阐明Utt-B抗纤维和抗癌作用的潜在机制.
主要方法:
- 用高脂肪饮食和用链毒素诱导的模型建立了MASH和MASH诱导的HCC的小鼠模型.
- Utt-B是通过腹膜内给药的,其效果是通过组织学分析 (H&E,油红O,Sirius红,马森三色素),蛋白质表达 (RT-qPCR,免疫阻塞) 和纳米链n-Counter分析来评估的.
- 进行了扩散和亡标记的评估,并使用R和GraphPad-Prism进行了统计分析.
主要成果:
- Utt-B显著改善了MASH的病理特征,包括肥胖症,肝细胞膨胀和炎症 (NAS <2,p <0.0001).
- Utt-B上调的自标志物 (ATG-7,Beclin-1,LC3-II) 和下调的α-SMA,表明肝星细胞激活减少.
- 通过阻碍纤维化,抑制增殖和诱导亡 (NAS <3, p <0.01),Utt-B抑制了MASH向HCC的进展.
结论:
- 乌特罗斯B对MASH和MASH诱导的HCC具有显著的治疗潜力.
- 通过调节自,纤维化和细胞死亡途径,Utt-B有效地逆转MASH病理,并阻止其发展为癌症.
- 这些发现将Utt-B定位为治疗MASH和相关肝癌的有希望的候选药物,解决了严重的未满足的医疗需求.
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