Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.
NHFPC Key Laboratory of Combined Multi-Organ Transplantation, Hangzhou 310003, China.
Biomed Res Int. 2020 Mar 14;2020:3635787. doi: 10.1155/2020/3635787. eCollection 2020.
Nanosecond pulsed electric field (nsPEF) has emerged as a promising tool for hepatocellular carcinoma ablation recently. However, little is known about how nsPEF affects liver regeneration while being applied to eliminate liver lesions. Besides, the impact of nsPEF ablation on liver function should also be taken into consideration in the process. In this paper, we study the impact of nsPEF ablation on liver function by the measurement of serum levels of AST and ALT as well as liver regeneration and relevant molecular mechanisms in vivo. We found that mouse liver function exhibited a temporary injury without weight loss after ablation. In addition, local hepatic nsPEF ablation promoted significant proliferation of hepatocytes of the whole liver with an increase in HGF level. Moreover, the proliferation of hepatocytes was dramatically inhibited by the inhibitor of c-Met. Of interest, the periablational area is characterized by high level of PDGF and a large amount of activated hepatic stellate cells. Furthermore, neutralizing PDGF was able to significantly inhibit liver regeneration, the increased HGF level, and the accumulation of activated HSCs. Our findings demonstrated that nsPEF not only was a safe ablation approach but also could stimulate the regeneration of the whole liver through the activation of the HGF/c-Met pathway by upregulation of PDGF within the periablational zone.
纳秒脉冲电场（nsPEF）最近已成为一种很有前途的肝癌消融工具。然而，当应用于消除肝脏病变时，nsPEF 如何影响肝脏再生还知之甚少。此外，在这个过程中还应考虑 nsPEF 消融对肝功能的影响。在本文中，我们通过测量血清 AST 和 ALT 水平以及体内肝脏再生和相关分子机制来研究 nsPEF 消融对肝功能的影响。我们发现，消融后小鼠肝功能短暂受损，体重无下降。此外，局部肝 nsPEF 消融促进了整个肝脏的肝细胞显著增殖，HGF 水平升高。此外，c-Met 抑制剂显著抑制了肝细胞的增殖。有趣的是，围消融区的特点是 PDGF 水平高和大量激活的肝星状细胞。此外，中和 PDGF 能够显著抑制肝再生、增加的 HGF 水平和激活的 HSCs 的积累。我们的研究结果表明，nsPEF 不仅是一种安全的消融方法，而且还可以通过上调围消融区 PDGF 来激活 HGF/c-Met 通路，刺激整个肝脏的再生。
