改良桂枝甘草汤对EGFR突变NSCLC患者奥希替尼诱导心肌细胞焦亡的影响

doi:10.3760/cma.j.cn441417-20241010-11016

国际医药卫生导报 ›› 2025, Vol. 31 ›› Issue (11): 1845-1849.DOI: 10.3760/cma.j.cn441417-20241010-11016

改良桂枝甘草汤对EGFR突变NSCLC患者奥希替尼诱导心肌细胞焦亡的影响

龙惠东^1,2 郭若月² 周璟瑜² 林云恩³ 陈汉锐¹

¹广州中医药大学第一临床学院，广州 510168；²广州医科大学附属肿瘤医院中西医结合科，广州 510095；³广州医科大学附属肿瘤医院病理科，广州 510095

收稿日期:2024-10-10 出版日期:2025-06-01 发布日期:2025-06-14
通讯作者: 陈汉锐，Email：13760618850@139.com
基金资助:
广东省中医药局科研项目（20232116）；广东省医学科学技术研究基金（A2023226）；广州市卫生健康科技项目（20211A011091）；广州市中医药和中西医结合科技项目（20212A011024）；广东省医学会临床研究专项基金（A202301018）

The effect of modified Guizhi Gancao decoction on the induction of cardiomyocyte pyroptosis by osimertinib in EGFR mutant NSCLC patients

Long Huidong^1,2, Guo Ruoyue², Zhou Jinyu², Lin Yunen³, Chen Hanrui¹

¹First Clinical College, Guangzhou University of Chinese Medicine, Guanghzou 510168, China; ²Department of Integrative Medicine, Affiliated Cancer Hospital of Guangzhou Medical University Guangzhou 510095, China; ³Department of Pathology, Affiliated Cancer Hospital of Guangzhou Medical University, Guangzhou 510095, China

Received:2024-10-10 Online:2025-06-01 Published:2025-06-14
Contact: Chen Hanrui, Email: 13760618850@139.com
Supported by:
Guangdong Provincial Administration of Traditional Chinese Medicine Research Project (A20232116); Guangdong Medical Science and Technology Research Fund (A2023226); Guangzhou Health and Wellness Technology Project (20211A011091); Guangzhou Traditional Chinese Medicine and Integrated Traditional and Western Medicine Technology Project (20212A011024); Guangdong Medical Association Clinical Research Special Fund (A202301018)

摘要/Abstract

摘要：

目的　本研究旨在评估改良桂枝甘草汤对表皮生长因子受体（EGFR）突变的非小细胞肺癌（NSCLC）患者使用奥希替尼治疗后诱导心肌细胞焦亡的干预作用。方法　本研究为病例对照研究。选取2019年1月至2022年1月期间广州医科大学附属肿瘤医院收治的100例EGFR突变晚期NSCLC患者，根据是否联合应用改良桂枝甘草汤将患者分为对照组和中药组，每组50例。对照组男13例、女37例，年龄（69.16±4.61）岁，口服甲磺酸奥希替尼片80 mg，每日1次。中药组男12例、女38例，年龄（69.02±4.13）岁，予以奥希替尼联合改良桂枝甘草汤治疗，改良桂枝甘草汤每日1剂，分早晚2次服用，每21 d为1个疗程。两组疗程均为3个月。比较两组患者治疗前后心功能指标及血清焦亡相关蛋白的水平，评估中药干预效果。采用χ2检验、t检验进行统计分析。结果　治疗后，中药组患者的二尖瓣扩张早期的血流速度与心房收缩期峰值血流速度的比值（E/A）高于对照组（1.13±0.49比0.84±0.25），差异有统计学意义（t=3.728，P<0.001）；中药组患者的血清胱天蛋白酶-1、白细胞介素-1β（IL-1β）、IL-18水平均低于对照组［（52.67±6.02）pg/L比（60.75±6.05）pg/L、（42.35±2.43）pg/L比（58.55±3.01）pg/L、（37.22±3.32）ng/L比（50.44±4.11）ng/L］，差异均有统计学意义（t=6.694、29.611、17.693，P<0.001）。两组近期疗效比较，差异均无统计学意义（均P>0.05）。结论　奥希替尼联合改良桂枝甘草汤治疗EGFR突变的NSCLC患者，能够有效减少奥希替尼引起的心肌细胞焦亡反应，改善患者的心功能，增强靶向治疗的耐受性并改善预后。

关键词: 非小细胞肺癌, EGFR突变, 改良桂枝甘草汤, 奥希替尼, 心肌细胞焦亡

Abstract:

Objective　This study aims to assess the intervention effects of modified Guizhi Gancao decoction on cardiomyocyte pyroptosis induced by osimertinib treatment in patients with epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC). Methods　This is a case-control study. Selecting 100 patients with advanced EGFR mutant NSCLC admitted to the Affiliated Cancer Hospital of Guangzhou Medical University from January 2019 to January 2022, the patients were divided into a control group and a traditional Chinese medicine group based on whether they were treated with modified Guizhi Gancao decoction in combination, with 50 patients in each group. There were 13 males and 37 females in the control group, aged (69.16 ± 4.61) years, who were orally administered 80 mg of Axitinib Mesylate tablets once daily. There were 12 males and 38 females in the traditional Chinese medicine group, with an age of (69.02 ± 4.13) years, receiving osimertinib combined with modified Guizhi Gancao decoction. The modified Guizhi Gancao decoction was administered once daily in two doses (morning and evening), with each treatment cycle lasting 21 days. Both groups underwent treatment for 3 months. The cardiac function indicators and serum pyroptosis-related protein levels before and after treatment were compared between the two groups to evaluate the effects of TCM intervention. Statistical analysis was performed using χ² tests and t tests. Results　After treatment, the E/A ratio in the TCM group was higher than that in the control group [(1.13±0.49) points vs. (0.84±0.25) points], with a statistically significant difference (t=3.728, P<0.001). The serum levels of Caspase-1, interleukin-1β (IL-1β), and IL-18 in the TCM group were lower than those in the control group [(52.67±6.02) pg/L vs. (60.75±6.05) pg/L, (42.35±2.43) pg/L vs. (58.55±3.01) pg/L, (37.22±3.32) ng/L vs. (50.44±4.11) ng/L], with statistically significant differences (t=6.694, 29.611, 17.693, P<0.001). There were no statistically significant differences in recent efficacy between the two groups (all P>0.05). Conclusion　The combination of osimertinib and modified Guizhi Gancao decoction in treating EGFR mutant NSCLC patients effectively reduces the pyroptosis response induced by osimertinib, improves cardiac function, enhances the tolerance to targeted therapy, and improves prognosis.

Key words: Non-small cell lung cancer, , EGFR Mutation, , ModifiedGuizhi Gancao , decoction, , Osimertinib, , Pyroptosis of myocardial cells

龙惠东郭若月周璟瑜林云恩陈汉锐. 改良桂枝甘草汤对EGFR突变NSCLC患者奥希替尼诱导心肌细胞焦亡的影响 [J]. 国际医药卫生导报, 2025, 31(11): 1845-1849.

Long Huidong, Guo Ruoyue, Zhou Jinyu, Lin Yunen, Chen Hanrui.

The effect of modified Guizhi Gancao decoction on the induction of cardiomyocyte pyroptosis by osimertinib in EGFR mutant NSCLC patients [J]. International Medicine and Health Guidance News, 2025, 31(11): 1845-1849.

参考文献

[1]Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3): 209-249. DOI: 10.3322/caac.21660.

[2]Asamura H, Nishimura KK, Giroux DJ, et al. IASLC lung cancer staging project: the new database to inform revisions in the ninth edition of the TNM classification of lung cancer[J]. J Thorac Oncol, 2023, 18(5):564-575. DOI: 10.1016/j.jtho.2023.01.088.

[3]Zhang D, Liu X, Shen F, et al. Osimertinib versus comparator first-generation epidermal growth factor receptor tyrosine kinase inhibitors as first-line treatment in patients with advancedEGFR-mutated non-small cell lung cancer: a Chinese, multicenter, real-world cohort study[J]. Transl Lung Cancer Res, 2023, 12(11): 2229-2244. DOI: 10.21037/tlcr-23-577.

[4]Kunimasa K, Kamada R, Oka T, et al. Cardiac adverse events inEGFR-mutated non-small cell lung cancer treated with osimertinib[J]. JACC CardioOncol, 2020, 2(1):1-10. DOI: 10.1016/j.jaccao.2020.02.003.

[5]李东航,姚颐,耿庆.中国临床肿瘤学会肺癌诊疗指南(2018版)更新解读[J].临床外科杂志,2019,27(1):36-39. DOI:10.3969/j.issn.1005-6483.2019.01.010.

[6]Sun JM, Ahn MJ, Park MJ, et al. Accuracy of RECIST 1.1 for non-small cell lung cancer treated with EGFR tyrosine kinase inhibitors[J]. Lung Cancer, 2010, 69(1):105-109. DOI: 10.1016/j.lungcan.2009.09.014.

[7]Imyanitov EN, Iyevleva AG, Levchenko EV. Molecular testing and targeted therapy for non-small cell lung cancer: current status and perspectives[J]. Crit Rev Oncol Hematol, 2021, 157: 103194. DOI: 10.1016/j.critrevonc.2020.103194.

[8]Harrison PT, Vyse S, Huang PH. Rare epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer[J]. Semin Cancer Biol, 2020, 61:167-179. DOI: 10.1016/j.semcancer.2019.09.015.

[9]陈薪如,周彩存.肺癌内科治疗临床研究十年回顾和现状[J].实用肿瘤杂志,2024,39(3):209-218.DOI:10.13267/j.cnki.syzlzz.2024.033.

[10]董士超,霍小东,孙川,等.基于真实世界监测数据挖掘与分析奥希替尼上市后的不良反应信号[J].中国医院药学杂志,2022,42(6):642-646. DOI:10.13286/j.1001-5213. 2022.06.13.

[11]Popat S. Osimertinib as first-line treatment in EGFR-mutated non-small-cell lung cancer[J]. N Engl J Med, 2018, 378(2): 192-193. DOI: 10.1056/NEJMe1714580.

[12]Oyakawa T, Nakashima K, Naito T. Cardiac dysfunction caused by osimertinib[J]. J Thorac Oncol, 2017, 12(10): e159-e160. DOI: 10.1016/j.jtho.2017.05.016.

[13]Lee CS, Sharma S, Miao E, et al. A comprehensive review of contemporary literature for epidermal growth factor receptor tyrosine kinase inhibitors in non-small cell lung cancer and their toxicity[J]. Lung Cancer (Auckl), 2020, 11: 73-103. DOI: 10.2147/LCTT.S258444.

[14]Schiefer M, Hendriks LEL, Dinh T, et al. Current perspective: osimertinib-induced QT prolongation: new drugs with new side-effects need careful patient monitoring[J]. Eur J Cancer, 2018, 91:92-98. DOI: 10.1016/j.ejca.2017.12.011.

[15]安涛.肺癌靶向治疗药物的心血管毒性[J].中国肿瘤临床,2021,48(6):311-316.DOI:10.3969/j.issn.1000-8179.2021.06.557.

[16]李文标,徐缘博,沈隽吉,等.基于网络药理学和分子对接探讨炙黄芪拮抗阿霉素心肌损伤的机制研究[J].中药药理与临床,2022,38(1):110-118.DOI:10.13412/j.cnki.zyyl.20210622.002.

[17]于江,唐家杨,李帅,等.心力衰竭气虚证动物模型的建立与评价[J].中国实验方剂学杂志,2023,29(15):60-67.DOI:10.13422/j.cnki.syfjx.20230536.

[18]王荣,潘力,黄金玲.苓桂术甘汤治疗心血管疾病的作用机制研究进展[J].中草药,2024,55(9):3146-3156. DOI:10.7501/j.issn.0253-2670.2024.09.028.

[19]童恒力,钟凌云.不同姜制附子对急性心力衰竭大鼠血流动力学的影响[J].中华中医药杂志,2019,34(1):332-335.

[20]邱月清,王振涛,郭宗耀.炙甘草汤防治心血管疾病的实验与机制概述[J].中华中医药学刊,2024,42(4):125-129,后插31. DOI:10.13193/j.issn.1673-7717.2024.04.026.

[21]栾海蓉,董琦,代海兵,等.槲寄生联合RIPOC对大鼠心肌保护作用[J].中国医学创新,2019,16(36):33-36. DOI:10.3969/j.issn.1674-4985.2019.36.008.

[22]赵婧含,李雪,吴文轩,等.熟地黄的化学成分及药理作用研究进展[J].中医药学报,2023,51(6):110-114. DOI:10.19664/j.cnki.1002-2392.230137.

[23]雷紫琴,栾飞,高铭,等.细胞焦亡与心血管疾病的关系及中医药防治研究进展[J].中国中药杂志,2023,48(7):1779-1791. DOI:10.19540/j.cnki.cjcmm.20221219.601.

[24]Mangan MSJ, Olhava EJ, Roush WR, et al. Targeting the NLRP3 inflammasome in inflammatory diseases[J]. Nat Rev Drug Discov, 2018, 17(9): 688. DOI: 10.1038/nrd.2018.149.

[25]王栋,李芳赫,于雪,等. NLRP3炎症小体在心力衰竭中的作用及中医药干预的研究进展[J].中国中药杂志,2024,49(4):894-901. DOI:10.19540/j.cnki.cjcmm.20230915.406.

[26]Sokolova M, Ranheim T, Louwe MC, et al. NLRP3 inflammasome: a novel player in metabolically induced inflammation-potential influence on the myocardium[J]. J Cardiovasc Pharmacol, 2019, 74(4): 276-284. DOI: 10.1097/FJC.0000000000000704.

[27]刘金川,丁汉琳,李丽楠.七氟醚后处理对缺氧复氧诱导的H9C2心肌细胞焦亡及TXNIP/NLRP3通路的影响[J].中国免疫学杂志,2023,39(5):922-927. DOI:10.3969/j.issn.1000-484X.2023.05.005.

[28]王丽凤,任骏.NLRP3炎症小体与心脏骤停复苏后心肌缺血再灌注损伤的研究进展[J].生命科学,2023,35(11):1527-1534. DOI:10.13376/j.cbls/2023165.

改良桂枝甘草汤对EGFR突变NSCLC患者奥希替尼诱导心肌细胞焦亡的影响

The effect of modified Guizhi Gancao decoction on the induction of cardiomyocyte pyroptosis by osimertinib in EGFR mutant NSCLC patients

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

[1]	赵金鹏高呈飞吕晓东. 浸润性非小细胞肺癌患者水平裂分化情况及肿瘤边缘-水平裂距离与预后的关系 [J]. 国际医药卫生导报, 2025, 31(5): 761-765.
[2]	刘珍珍刘谩贾永庆杨美菊. miR-6884-5p在非小细胞肺癌中的表达及与肿瘤标志物的相关性 [J]. 国际医药卫生导报, 2025, 31(5): 766-770.
[3]	张洋王景景王博李小军. EGFR阳性的晚期NSCLC患者应用吉非替尼治疗的效果及安全性 [J]. 国际医药卫生导报, 2025, 31(11): 1905-1910.
[4]	张娟江一博阮稳稳. 替雷利珠单抗联合白蛋白紫杉醇和顺铂治疗老年晚期非小细胞肺癌脑转移患者的临床研究 [J]. 国际医药卫生导报, 2025, 31(1): 105-110.
[5]	马静蔺婷婷董宁霞吕文文. EGFR-TKI单药与传统化疗方案治疗进展期NSCLC安全性的网状meta分析 [J]. 国际医药卫生导报, 2024, 30(6): 897-902.
[6]	吴媛媛刘科齐艳丽童小华. 非小细胞肺癌组织中CLCA4的表达情况及与病理和预后的关系 [J]. 国际医药卫生导报, 2024, 30(6): 903-907.
[7]	程琳魏亚兰田霞. ALK突变晚期非小细胞肺癌靶向治疗耐药后帕博利珠单抗治疗的新探索 [J]. 国际医药卫生导报, 2024, 30(6): 908-912.
[8]	樊成涛鱼芳. 伏美替尼与吉非替尼治疗EGFR敏感突变的晚期非小细胞肺癌的临床效果 [J]. 国际医药卫生导报, 2024, 30(6): 913-917.
[9]	陈荔蕊苏照坤高亚娜. 延伸护理在非小细胞肺癌患者阿替利珠单抗免疫治疗中的应用效果 [J]. 国际医药卫生导报, 2024, 30(6): 918-922.
[10]	张前陈亮杨冉. 3D-CTBA精准定位应用于胸腔镜肺段切除术患者的临床价值 [J]. 国际医药卫生导报, 2024, 30(6): 923-927.
[11]	胡少博张娜莉程静梅. 血清KL-6水平与NSCLC患者PD-1相关免疫性肺炎的关联性 [J]. 国际医药卫生导报, 2024, 30(4): 602-605.
[12]	张莉君秦玮珣秦彩娟谢燕华. 穴位埋线联合健脾清肺汤对化疗后脾肺气虚证非小细胞肺癌患者的效果 [J]. 国际医药卫生导报, 2024, 30(24): 4132-4136.
[13]	张田赵丹. 信迪利单抗联合重组人血管内皮抑制素治疗晚期非小细胞肺癌的临床研究 [J]. 国际医药卫生导报, 2024, 30(24): 4137-4140.
[14]	王淑红常英张莉霞. 伏美替尼联合GC化疗方案对非小细胞肺癌患者的疗效观察 [J]. 国际医药卫生导报, 2024, 30(24): 4141-4145.
[15]	张臣王勇赵山虎. 非小细胞肺癌根治术后Ⅱ类切口感染的影响因素分析 [J]. 国际医药卫生导报, 2024, 30(24): 4146-4149.