Research Article

中华支睾吸虫肝吸虫CsHscB改善硬化性胆管炎小鼠模型中的胆汁淤积性肝纤维化

卷 24, 期 4, 2024

发表于: 17 May, 2023

页: [505 - 515] 页: 11

弟呕挨: 10.2174/1566524023666230418111949

价格: $65

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摘要

背景:原发性硬化性胆管炎(PSC)是一种以炎性纤维化为特征的慢性胆汁淤积性肝病,通常累及整个胆道。然而,治疗这种疾病的治疗方法非常有限。我们前期的研究发现,肝吸虫华支睾吸虫的脂质蛋白rCsHscB具有完全的免疫调节能力。因此,我们研究了rCsHscB在外源药物3,5-二氧羰基-1,4-二氢碰撞碱(DDC)诱导的硬化性胆管炎小鼠模型中的作用,以探讨该蛋白是否对PSC具有潜在的治疗价值。 方法:小鼠灌胃0.1% DDC,灌胃4周后给予CsHscB (30 μg/只,腹腔注射,3 d 1次);对照组在正常饮食条件下给予等量PBS或CsHscB。4周处死小鼠,观察胆道增生、纤维化和炎症情况。 结果:rCsHscB治疗可减轻ddc诱导的肝充血和肝肿大,显著降低血清AST和ALT水平上调。与单独喂食DDC的小鼠相比,给DDC喂食rCsHscB显著降低了胆管细胞的增殖和促炎细胞因子的产生。此外,rCsHscB治疗显示肝脏α-SMA和其他肝纤维化标志物(马松染色、羟脯氨酸含量和胶原沉积)的表达降低。更有趣的是,经rCsHscB处理的ddc喂养的小鼠PPAR-γ表达显著上调,与对照小鼠相似,这表明PPAR-γ信号参与了rCsHscB的保护作用。 结论:总体而言,我们的数据显示rCsHscB可减缓DDC诱导的胆汁淤积性纤维化的进展,并支持操纵寄生虫衍生分子治疗某些免疫介导疾病的潜力。

关键词: CsHscB蛋白,华支睾吸虫,DDC,胆汁淤积性肝纤维化,PPAR-γ,免疫调节。

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