Panax notoginseng saponins promote liver regeneration through activation of the PI3K/AKT/mTOR cell proliferation pathway and upregulation of the AKT/Bad cell survival pathway in mice

Panax notoginseng saponins promote liver regeneration through activation of the PI3K/AKT/mTOR cell proliferation pathway and upregulation of the AKT/Bad cell survival pathway in mice
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三七皂苷通过激活 PI3K/AKT/mTOR 细胞增殖途径和上调 AKT/Bad 细胞存活途径促进小鼠肝再生

DOI:
10.1186/s12906-019-2536-2
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发表时间:
2019-06-10
影响因子:
--
通讯作者:
Yuan, Fangchao
Yuan, Fangchao
中科院分区:
医学3区
文献类型:
--
作者:
Zhong, Hua;Wu, Hao;Yuan, Fangchao

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背景肝脏的再生能力对于严重肝损伤、肿瘤切除或活体肝移植后的宿主存活至关重要。据报道,三七皂苷(PNS)在器官损伤中发挥保护作用。本研究旨在评价PNS对肝再生(LR)和肝部分切除术(PH)损伤的影响。方法对C57BL/ 6j小鼠进行70%部分PH处理。以肝重/体重、血清谷丙转氨酶(ALT)和天冬氨酸转氨酶(AST)水平及细胞增殖情况评估LR,并采用Western blot分析相关细胞信号。结果不同浓度的PNS对肝细胞增殖有促进作用。与正常对照(NC)组相比,PNS组小鼠在PH后第2天和第7天肝脏/体重比均显著升高(P< 0.05),血清ALT和AST水平显著降低(P< 0.05)。组织学分析显示,PNS组在PH后2 d和7 d增殖细胞核抗原(PCNA)的表达显著高于NC组(P< 0.05)。机制上,PNS可激活AKT/mTOR细胞增殖通路和AKT/Bad细胞存活通路,促进肝细胞增殖,抑制凋亡(P< 0.05)。结论spns通过激活PI3K/AKT/mTOR促进小鼠肝脏再生,上调AKT/Bad细胞通路。
BackgroudThe regenerative capacity of the liver is crucial for the host to survive after serious hepatic injuries, tumor resection, or living donor liver transplantation.Panax notoginsengsaponins (PNS) have been reported to exert protective effects during organ injuries. The present study aimed to evaluate the effect of PNS on liver regeneration(LR) and on injuries induced by partial hepatectomy (PH).MethodsWe performed 70% partial PH on C57BL/6 J mice treated with or without PNS. LR was estimated by liver weight/body weight, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and cell proliferation, and the related cellular signals were analyzed by Western blot.ResultsDifferent concentrations of PNS promoted hepatocyte proliferation in vitro. Mice in the PNS group showed higher liver/body weight ratios at 2 d and 7 d (P< 0.05) after PH and lower levels of serum ALT and AST (P< 0.05) compared to those of mice in the normal control (NC) group. Histological analysis showed that the expression of proliferating cell nuclear antigen(PCNA) at 2 d and 7 d after PH was significantly higher in the PNS group than in the NC group (P< 0.05). Mechanistically, the AKT/mTOR cell proliferation pathway and AKT/Bad cell survival pathway were activated by PNS, which accelerated hepatocyte proliferation and inhibited apoptosis (P< 0.05).ConclusionsPNS promoted liver regeneration through activation of PI3K/AKT/mTOR and upregulated the AKT/Bad cell pathways in mice.