Department of Gastroenterology, Chengdu Integrated TCM&Western Medicine Hospital, Chengdu University of Traditional Chinese Medicine, Chengdu 610059, China.
School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China.
Molecules. 2022 Nov 15;27(22):7890. doi: 10.3390/molecules27227890.
The promotion of liver regeneration is crucial to avoid liver failure after hepatectomy. polysaccharide (ASP) and polysaccharide (AMP) have been identified as being associated with hepatoprotective effects. However, their roles and specific mechanisms in liver regeneration remain to be elucidated. In the present study, it suggested that the respective use of ASP or AMP strikingly promoted hepatocyte proliferation in vitro with a wide range of concentrations (from 12.5 μg/mL to 3200 μg/mL), and a stronger promoting effect was observed in combined interventions. A significantly enhanced liver/body weight ratio (4.20%) on day 7 and reduced serum transaminase (ALT 243.53 IU/L and AST 423.74 IU/L) and total bilirubin (52.61 IU/L) levels on day 3 were achieved by means of ASP-AMP administration after partial hepatectomy in mice. Metabonomics showed that differential metabolites were enriched in glycolysis with high expression of beta-d-fructose 6-phosphate and lactate, followed by significantly strengthened lactate secretion in the supernatant (0.54) and serum (0.43) normalized to control. Upon ASP-AMP treatment, the knockdown of hexokinase 2 (HK2) or inhibited glycolysis caused by 2-deoxy-d-glucose decreased hepatocyte proliferation in vitro and in vivo. Furthermore, pathway analysis predicted the role of JAK2/STAT3 pathway in ASP-AMP-regulated liver regeneration, and phosphorylation of JAK2 and STAT3 was proven to be elevated in this promoting process. Finally, downregulated expression of HK2, an attenuated level of lactate secretion, and reduced hepatocyte proliferation were displayed when STAT3 was knocked out in vitro. Therefore, it can be concluded that ASP-AMP accelerated liver regeneration and exerted a hepatoprotective effect after hepatectomy, in which the JAK2/STAT3/HK2 pathway was actively involved in activating glycolysis.
促进肝再生对于避免肝切除术后肝衰竭至关重要。多糖（ASP）和多糖（AMP）已被确定与肝保护作用有关。然而，它们在肝再生中的作用和具体机制仍有待阐明。在本研究中，研究表明，单独使用 ASP 或 AMP 在体外以广泛的浓度（从 12.5μg/mL 到 3200μg/mL）显著促进肝细胞增殖，并且联合干预观察到更强的促进作用。通过 ASP-AMP 给药，在小鼠部分肝切除术后第 7 天观察到肝/体重比（4.20%）显著提高，第 3 天血清转氨酶（ALT 243.53IU/L 和 AST 423.74IU/L）和总胆红素（52.61IU/L）水平降低。代谢组学表明，差异代谢物在糖酵解中富集，β-d-果糖 6-磷酸和乳酸的高表达，随后上清液（0.54）和血清（0.43）中乳酸分泌明显增强，与对照相比归一化。在 ASP-AMP 处理后，敲低己糖激酶 2（HK2）或用 2-脱氧-d-葡萄糖抑制糖酵解会降低体外和体内的肝细胞增殖。此外，途径分析预测 JAK2/STAT3 途径在 ASP-AMP 调节肝再生中的作用，并且在这个促进过程中证明 JAK2 和 STAT3 的磷酸化水平升高。最后，在体外敲除 STAT3 时，HK2 的表达下调，乳酸分泌水平降低，肝细胞增殖减少。因此，可以得出结论，ASP-AMP 加速肝再生并在肝切除术后发挥肝保护作用，其中 JAK2/STAT3/HK2 途径积极参与激活糖酵解。
