基于SIRT5/AMPK/mTOR/eIF2a信号轴探讨益气化瘀解毒方干预肝癌细胞能量代谢平衡的作用及机制

肿瘤细胞通过代谢重编程、自噬和蛋白质翻译高效供应能量和生物大分子，促进其快速增殖生长、侵袭转移。SIRT5/AMPK/mTOR/eIF2a信号轴可能发挥着关键作用，但其机制尚未明确。“癌毒致虚、毒瘀互结、肝脾失调”与肝癌细胞能量代谢紧密相关。前期研究揭示“益气化瘀解毒方”能稳定体重和瘤体、抗复发转移而呈现“带瘤生存”特点。由此提出科学假说：“癌毒致虚”启动肝癌细胞自噬、蛋白质翻译和代谢再编程，“益气化瘀解毒方”攻补兼施，干预SIRT5/AMPK/mTOR/eIF2a信号轴，从而打破其能量和生物合成平衡，拮抗肝癌侵袭转移，实现“带瘤生存”。为此，以质粒转染技术构建HBx/HepG2细胞模型和鼠肝原位移植模型，基于SIRT5/AMPK/mTOR/eIF2a信号轴，探讨“益气化瘀解毒方”干预能量代谢和生物合成机制，为寻找打破肝癌细胞代谢平衡和代谢高速而拮抗其侵袭转移的有效方药提供新思路。

Tumor cells maintain energy balance through metabolic reprogramming, autophagy and protein translation, which is closely related to invasion and metastasis. SIRT5/AMPK/mTOR/eIF2a axis exerts a significant role in regulating it. However, its mechanism is not clear. "Deficiency caused by cancer toxin, internal stagnation of toxin and imbalance of liver and spleen" are closely related to the energy metabolism of liver cancer cells. Previous studies have shown that Yiqihuayujiedu prescription can stabilize body weight and tumor and resist recurrence and metastasis of mouse, showing the characteristics of "survival with tumor". Therefore, the scientific hypothesis is put forward: "deficiency caused by cancer toxin" starts the process of autophagy, protein translation and metabolic reprogramming of liver cancer cells, and Yiqihuayujiedu prescription attacks and tonifies, interferes with the SIRT5/AMPK/mTOR/eIF2a axis, so as to break its energy balance, antagonize the invasion and metastasis of liver cancer. Thus, immunological and molecular biological techniques were used to construct HBx/HepG2 cell model and orthotopic liver transplantation model by plasmid transfection technology. The effect and mechanism of Yiqihuayujiedu prescription on cell energy metabolism through SIRT5/AMPK/mTOR/eIF2a axis were discussed, which provides a new idea for finding effective drugs to break the energy balance of hepatocellular carcinoma antagonize invasion and metastasis.