Department of Infectious Diseases, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong, China; School of Pharmacy, Rutgers University, Piscataway, NJ, USA.
University of Kansa Medical Center, Kansas City, KS, USA.
Dig Liver Dis. 2018 Feb;50(2):175-180. doi: 10.1016/j.dld.2017.08.023. Epub 2017 Aug 12.
The leading cause of acute liver failure (ALF) is hepatotoxicity from acetaminophen (APAP) overdose. However, limited options are available to treat this ALF so stimulating liver regeneration maybe a potential treatment. Our previous study has shown that fibroblast growth factor 15 (FGF15) plays a crucial role in liver regeneration, but the roles of FGF15 in liver injury and repair following APAP-overdose are unknown. In this study, treatment of FGF15 knockout (KO) male mice with APAP at 200, 250, or 300mg/kg significantly increased the degree of liver injury compared to wild type (WT) mice. To determine the effects of FGF15 deficiency on liver repair following APAP overdose, a similar degree of liver injury was first obtained 24h after treatment of WT and Fgf15 KO mice with APAP at different dosage. Fgf15 KO mice did not differ from WT mice in liver repair following similar degree of liver injury. In conclusion, we showed that FGF15 deficiency renders mice more susceptible to APAP-induced liver injury but did not seem to affect liver repair or regeneration. This study suggests that in contrast to the critical role that FGF15 plays in promoting liver regeneration following partial hepatectomy, this intestine factor is less involved in liver repair after APAP-induced liver injury.
急性肝衰竭（ALF）的主要原因是对乙酰氨基酚（APAP）过量引起的肝毒性。然而，治疗这种 ALF 的选择有限，因此刺激肝再生可能是一种潜在的治疗方法。我们之前的研究表明，成纤维细胞生长因子 15（FGF15）在肝再生中起着至关重要的作用，但 FGF15 在 APAP 过量后肝损伤和修复中的作用尚不清楚。在这项研究中，用 200、250 或 300mg/kg 的 APAP 治疗 FGF15 敲除（KO）雄性小鼠，与野生型（WT）小鼠相比，显著增加了肝损伤的程度。为了确定 FGF15 缺乏对 APAP 过量后肝修复的影响，首先用不同剂量的 APAP 处理 WT 和 Fgf15 KO 小鼠 24 小时后，获得了相似程度的肝损伤。在相似程度的肝损伤后，Fgf15 KO 小鼠与 WT 小鼠在肝修复方面没有差异。总之，我们表明 FGF15 缺乏使小鼠更容易受到 APAP 诱导的肝损伤，但似乎不会影响肝修复或再生。这项研究表明，与 FGF15 在部分肝切除后促进肝再生中发挥的关键作用相反，这种肠因子在 APAP 诱导的肝损伤后肝修复中的参与程度较低。
