Pretreatment of artesunate promoted hepatocyte proliferation by activating the PI3K/Akt/mTOR signaling pathway in mice.

Acta cirurgica brasileira Pub Date : 2024-10-25 eCollection Date: 2024-01-01 DOI:10.1590/acb394324
Changyou Lu, Xinkai Li, Chao Fang, Chuntao Li, Yunke Xu, Yong Guo
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Abstract

Purpose: Artesunate (ART) has been implicated in regulating the many processes of liver injury, but its roles in liver regeneration still need to be illustrated.

Methods: In the present study, ART was used to pretreat hepatocyte cell line NCTC1469 to study the effect of ART on hepatocyte proliferation in vitro. Furthermore, the potency of ART as a regimen to promote liver regeneration and restore liver function was evaluated following partial hepatectomy (PH) on C57BL/6 mice.

Results: ART concentration-dependently promoted hepatocyte proliferation and reduced apoptosis. Cell cycle and Ki-67 immunohistochemical analyses demonstrated that ART supplementation promoted the proliferation of hepatocytes and accelerated liver regeneration. Our results provided evidence that ART improved liver function in a dose-dependent manner, as indicated by decreased serum alanine aminotransferase, aspartate aminotransferase, and increased albumin, and hepatocyte growth factor levels in PH mice. Meanwhile, ART promoted the PI3K/Akt/mTOR signaling in NCTC1469 cells and liver tissue of PH mice. In addition, PI3K inhibitor LY294002 blocked the promotion effect of ART on hepatocyte proliferation and cell cycle progression.

Conclusion: ART promoted hepatocyte proliferation via activation of the PI3K/Akt/mTOR pathway, which was beneficial to liver regeneration of PH-induced liver injury.

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青蒿琥酯预处理通过激活 PI3K/Akt/mTOR 信号通路促进小鼠肝细胞增殖。
目的:青蒿琥酯(ART)与调节肝损伤的许多过程有关,但其在肝再生中的作用仍有待说明:本研究使用 ART 对肝细胞系 NCTC1469 进行预处理,以研究 ART 对体外肝细胞增殖的影响。此外,在对C57BL/6小鼠进行部分肝切除术(PH)后,评估了ART作为促进肝再生和恢复肝功能的方案的有效性:ART具有浓度依赖性,能促进肝细胞增殖并减少细胞凋亡。细胞周期和 Ki-67 免疫组化分析表明,补充 ART 可促进肝细胞增殖并加速肝脏再生。我们的研究结果证明,抗逆转录病毒疗法能以剂量依赖的方式改善肝功能,PH 小鼠血清丙氨酸氨基转移酶、天冬氨酸氨基转移酶降低,白蛋白和肝细胞生长因子水平升高。同时,抗逆转录病毒疗法促进了NCTC1469细胞和PH小鼠肝组织中的PI3K/Akt/mTOR信号转导。此外,PI3K抑制剂LY294002阻断了ART对肝细胞增殖和细胞周期进展的促进作用:结论:ART通过激活PI3K/Akt/mTOR通路促进肝细胞增殖,有利于PH诱导的肝损伤的肝再生。
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