小剂量依托咪酯辅助丙泊酚麻醉诱导对肝细胞癌术后预后影响及机制分析

摘要/Abstract

摘要： 目的：分析小剂量依托咪酯（etomidate,ETO）辅助丙泊酚（propofol ,PRO）全静脉麻醉诱导对肝细胞癌（hepatocellular carcinoma ,HCC）患者预后影响并探索潜在生物学机制。
方法：选取阜阳市肿瘤医院2021年1月至2023年1月收治的84例HCC患者。根据随机数字表法将患者分为对照组（n=42）和实验组（n=42）,对照组采用PRO全静脉麻醉诱导,实验组采用小剂量ETO辅助PRO全静脉麻醉诱导。采用Kaplan-Meier法生存分析。通过Cox回归模型单因素和多因素分析确定ETO与HCC患者预后关系。通过生物信息学、微阵列数据、酶联免疫吸附测定及分子对接和动力学模型探索ETO在HCC根治性切除术患者麻醉诱导中潜在生物学机制。
结果：实验组患者无复发生存和总生存均高于对照组患者（均P<0.05）。Cox回归模型分析显示ETO是HCC患者复发及死亡的独立保护因素（均P<0.05）,肿瘤分期和CD34是HCC患者复发及死亡的独立危险因素（均P<0.05）。微阵列数据结果显示共有143个差异表达基因,主要富集在造血祖细胞分化的负向调节、雷帕霉素机制靶蛋白（mechanistic target of rapamycin,mTOR）、p53、血管内皮生长因子A和血管内皮生长因子受体2（vascular endothelial growth factor A and vascular endothelial growth factor receptor 2,VEGFA VEGFR2）和白细胞介素-24（interleukin-24,IL-24）信号通路中。PPI网络证实CD34是ETO抗HCC核心靶基因。分子对接和动力学模型证实ETO能与CD34蛋白稳定结合,结合自由能为-29.278 kJ/mol。Cox回归模型分析显示ETO是HCC患者复发及死亡的独立保护因素（均P<0.05）,肿瘤分期和CD34是HCC患者复发及死亡的独立危险因素（均P<0.05）。
结论：HCC根治性切除术患者小剂量ETO辅助PRO全静脉麻醉诱导方案能更好改善预后,可能与调控CD34表达有关。

关键词: 依托咪酯, 丙泊酚, 肝细胞癌, 根治性切除术, 预后

Abstract: Objective: To analyze the prognostic impact of low-dose etomidate (ETO) assisted propofol (PRO) induction of total intravenous anesthesia on patients with hepatocellular carcinoma (HCC) and to explore the underlying biological mechanisms.
Methods: Eighty-four HCC patients admitted to our hospital from January 2021 to January 2023 were selected. The patients were divided into a control group (n=42) and an experimental group (n=42) according to the randomized numerical table method; the control group was induced by PRO total intravenous anesthesia, and the experimental group was induced by a small dose of ETO-assisted PRO total intravenous anesthesia. The Kaplan-Meier method was employed for survival analysis.The relationship between ETO and the prognosis of HCC patients was determined by univariate and multivariate Cox regression model. Potential biological mechanisms of ETO in HCC radical resection patients were explored by bioinformatics, microarray data, enzyme-linked immunosorbent assay and molecular docking and kinetic modeling.The relationship between ETO and the prognosis of HCC patients was determined by univariate and multivariate Cox regression model.
Results: The recurrence-free survival and overall survival of patients in the experimental group were higher than those of patients in the control group (all P<0.05). Cox regression model analysis showed that ETO was an independent protective factor for recurrence and death in HCC patients (all P<0.05), and tumor stage and CD34 were independent risk factors for recurrence and death in HCC patients (all P<0.05). The results of microarray data showed a total of 143 differentially expressed genes, which were mainly enriched in signaling pathways such as negative regulation of hematopoietic progenitor cell differentiation, mechanistic target of rapamycin(mTOR), p53, vascular endothelial growth factor A and vascular endothelial growth factor receptor 2(VEGFA ,VEGFR2), and interleukin-24(IL-24). The PPI network confirmed that CD34 was a core target gene of ETO anti-HCC. Molecular docking and kinetic modeling confirmed that ETO could bind stably to CD34 protein with a binding free energy of -29.278 kJ/mol.Cox regression model analysis showed that ETO was an independent protective factor for recurrence and death in HCC patients (all P<0.05), and tumor stage and CD34 were independent risk factors for recurrence and death in HCC patients (all P<0.05).
Conclusion: Small-dose ETO-assisted PRO total intravenous anesthesia induction regimen in patients undergoing radical resection for HCC improves prognosis better and may be related to modulation of CD34 expression.

Key words: Etomidate, Propofol, Hepatocellular carcinoma, Radical resection, Prognosis

翟蕊, 于立春, 李宏祥, 翟永亚. 小剂量依托咪酯辅助丙泊酚麻醉诱导对肝细胞癌术后预后影响及机制分析[J]. 肝癌电子杂志, 2025, 12(4): 20-29.

Zhai Rui, Yu Lichun, Li Hongxiang, Zhai Yongya. Effect and mechanism analysis of low-dose ETO in adjuvant to PRO anesthesia induction for postoperative prognosis of hepatocellular carcinoma[J]. Electronic Journal of Liver Tumor, 2025, 12(4): 20-29.

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