在肝毒性实验模型中慢性肝损伤的动态
Piotr Czekaj1, Mateusz Król1, Emanuel Kolanko1
1Department of Cytophysiology, Chair of Histology and Embryology, Faculty of Medical Sciences in Katowice, Medical University of Silesia in Katowice, 40-752 Katowice, Poland.
Frontiers in bioscience (Landmark edition)
|May 31, 2023
概括
在动物模型中,碳四化物 (CCl4) 诱导肝纤维化比D-银胺 (D-GalN) 更快. CCl4模型为慢性肝病 (CLD) 干预提供了两个治疗窗口.
科学领域:
- 比较病理学比较病理学
- 毒理学 毒理学 毒理学
- 疾病的动物模型.
背景情况:
- 慢性肝病 (CLD) 带来了重大的临床挑战,目前没有治疗方法来阻止纤维化进展.
- 实验模型对于评估CLD疗法至关重要,但它们的动态根据诱导方法大大不同.
- 了解这些模型动态是选择肝纤维化适当干预措施的关键.
研究的目的:
- 为了比较BALB/c小鼠和具有CLD的Sprague Dawley大鼠病理变化的进展动态.
- 在CCl4-和D-GalN诱导的CLD模型中定义肝纤维化的发病和持续时间.
- 在这些动物肝纤维化模型中确定治疗干预的最佳时间.
主要方法:
- 在小鼠和老鼠中使用碳四化物 (CCl4) 或D-银胺 (D-GalN) 通过腹腔内注射诱导CLD.
- 在12周内定期采集血液和肝脏样本进行分析.
- 通过全血细胞计,肝功能测试,组织病理学和基因表达分析评估肝损伤和纤维化进展.
主要成果:
- 在小鼠和大鼠中,CCl4比D-GalN更快地诱导肝纤维化进展.
- 在CCl4的2-4周之间观察到早期纤维化,并在6周前确立纤维化.
- 后来D-GalN诱导纤维化,在4-10周出现初始症状,并在12周后在老鼠中出现不完全的肝硬化.
结论:
- CCl4模型比D-GalN模型表现出更大的纤维化动态,提供不同的治疗干预窗口 (4周前和8周后).
- D-GalN诱导的动物模型不太适合研究肝纤维化,因为化时间长,效果较弱.
- 该研究提供了对选择和优化用于CLD治疗研究的动物模型至关重要的比较分析.
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