芪参益气滴丸对索拉非尼诱导大鼠心肌损伤的改善作用及其机制

doi:10.13481/j.1671-587X.20260202

吉林大学学报(医学版) ›› 2026, Vol. 52 ›› Issue (2): 308-317.doi: 10.13481/j.1671-587X.20260202

• 基础研究 • 上一篇

芪参益气滴丸对索拉非尼诱导大鼠心肌损伤的改善作用及其机制

唐峥^1,²,刘薇³,胡红民³,赖琦^1,²,石妍^1,²,刘盛权³,杨军³,褚春^1,²()

^1.南华大学药学院，湖南衡阳 421001
^2.南华大学衡阳医学院附属第二医院药剂科，湖南衡阳 421001
^3.南华大学衡阳医学院附属第一医院心内科，湖南衡阳 421001

收稿日期:2025-03-23 接受日期:2025-06-12 出版日期:2026-03-28 发布日期:2026-04-15
通讯作者: 褚春 E-mail:1996020012@usc.edu.cn
作者简介:唐峥（2002-），男，湖南省永州市人，在读硕士研究生，主要从事临床药理学方面的研究。
基金资助:
国家自然科学基金项目(82074236);湖南省科技厅自然科学基金青年基金项目(2022JJ40399);湖南省卫健委临床重大专项项目(20201913)

Improvement effect of Qishen Yiqi dropping pills on myocardium injury in rats induced by sorafenib and its mechanism

Zheng TANG^1,²,Wei LIU³,Hongmin HU³,Qi LAI^1,²,Yan SHI^1,²,Shengquan LIU³,Jun YANG³,Chun CHU^1,²()

^1.School of Pharmaceutical Science，University of South China，Hengyang 421001，China
^2.Department of Pharmacy，Second Affiliated Hospital，Hengyang Medical School，University of South China，Hengyang 421001，China
^3.Department of Cardiology，First Affiliated Hospital，Hengyang Medical School，University of South China，Hengyang 421001，China

Received:2025-03-23 Accepted:2025-06-12 Online:2026-03-28 Published:2026-04-15
Contact: Chun CHU E-mail:1996020012@usc.edu.cn

摘要/Abstract

摘要：

目的探讨芪参益气（QSYQ）滴丸对索拉非尼（SOR）诱导大鼠心肌损伤的保护作用，并阐明其可能的作用机制。方法取40只SD大鼠随机分为对照组、SOR组、SOR+QSYQ组和SOR+铁死亡抑制剂1（Fer-1）组，每组10只。SOR组、SOR+QSYQ组和SOR+Fer-1组大鼠每日腹腔注射SOR（50 mg·kg^-1），持续4周；SOR+QSYQ组大鼠每日灌胃QSYQ滴丸（300 mg·kg^-1）；SOR+Fer-1组大鼠自SOR给药前1天起每日腹腔注射Fer-1（2 mg·kg^-1）。干预结束后，采用试剂盒检测各组大鼠血清中肌酸激酶同工酶（CK-MB）水平，超声心动图评估各组大鼠心功能左室射血分数（LVEF）和左心室短轴缩短率（LVFS），记录大鼠心脏质量和体质量并计算心脏指数。采用HE染色法观察各组大鼠心肌组织形态表现，试剂盒测定各组大鼠心肌组织中铁离子、谷胱甘肽（GSH）、丙二醛（MDA）和活性氧（ROS）水平，Western blotting法检测各组大鼠心肌组织中酰基辅酶A合成酶长链家族成员4（ACSL4）、溶质载体家族7成员11（SLC7A11）和谷胱甘肽过氧化物酶4（GPX4）蛋白表达水平。另取H9c2心肌细胞，分为对照组、SOR组、SOR+QSYQ组和SOR+Fer-1组。采用细胞计数试剂盒8（CCK-8）法测定各组细胞存活率，Western blotting法检测各组细胞中ACSL4和GPX4蛋白表达水平。结果与对照组比较，SOR组大鼠血清中CK-MB水平明显升高（P<0.05），LVEF和LVFS明显降低（P<0.05）；与SOR组比较，SOR+QSYQ组和SOR+Fer-1组大鼠血清中CK-MB水平均明显降低（P<0.05），LVEF明显升高（P<0.05）。与对照组比较，SOR组大鼠心肌纤维排列紊乱，间隙扩大；与SOR组比较，SOR+QSYQ组和SOR+Fer-1组大鼠心肌细胞损伤程度减轻，心肌纤维排列较整齐。与对照组比较，SOR组大鼠心肌组织中铁离子、MDA和ROS水平明显升高（P<0.05），GSH水平明显降低（P<0.05）；与SOR组比较，SOR+QSYQ组和SOR+Fer-1组大鼠心肌组织中铁离子和ROS水平明显降低（P<0.05），GSH水平明显升高（P<0.05）。与对照组比较，SOR组大鼠心肌组织中ACSL4蛋白表达水平明显升高（P<0.05），SLC7A11和GPX4蛋白表达水平明显降低（P<0.05）；与SOR组比较，SOR+QSYQ组和SOR+Fer-1组大鼠心肌组织中SLC7A11及GPX4蛋白表达水平明显升高（P<0.05），ACSL4蛋白表达水平明显降低（P<0.05）。与0 μmol·L^-1 SOR组比较，加入更高浓度SOR后各组H9c2细胞存活率均明显降低（P<0.05）；与SOR组细胞比较，不同浓度QSYQ组细胞存活率均明显升高（P<0.05），其中1 mg·L^-1 QSYQ干预组细胞存活率最高。与对照组比较，SOR组H9c2心肌细胞中ACSL4蛋白表达水平明显升高（P<0.05），GPX4蛋白表达水平明显降低（P<0.05）；与SOR组比较，SOR+QSYQ组和SOR+Fer-1组细胞中ACSL4蛋白表达水平明显降低（P<0.05），GPX4蛋白表达水平明显升高（P<0.05）。结论 QSYQ滴丸可减轻SOR诱导的大鼠心肌损伤，其机制可能与抑制心肌细胞铁死亡有关。

关键词: 芪参益气滴丸, 索拉非尼, 铁死亡, 心肌损伤, 氧化应激

Abstract:

Objective To discuss the protective effect of Qishen Yiqi （QSYQ） dropping pill against sorafenib （SOR）-induced myocardium injury in the rats， and to clarify its possible mechanism. Methods Forty SD rats were randomly divided into control group， SOR group， SOR+QSYQ group， and SOR+ferroptosis inhibitor 1 （Fer-1） group， with 10 rats in each group. The rats in SOR group， SOR+QSYQ group， and SOR+Fer-1 group were intraperitoneally injected with SOR （50 mg·kg^-1） daily for 4 weeks； the rats in SOR+QSYQ group were intragastrically administered with QSYQ dropping pill （300 mg·kg^-1） daily； the rats in SOR+Fer-1 group were intraperitoneally injected with Fer-1 （2 mg·kg^-1） daily starting from 1 d before SOR administration. After the intervention， kits were used to detect the levels of creatine kinase isoenzyme-MB （CK-MB） in serum of the rats in various groups； echocardiography was used to evaluate the left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （LVFS） of the rats in various groups； the heart mass and body mass of the rats were recorded， and the cardiac index was calculated. HE staining was used to observe the morphology of myocardium tissue of the rats in various groups； kits were used to detect the levels of iron ion， glutathione （GSH）， malondialdehyde （MDA）， and reactive oxygen species （ROS） in the myocardium tissue of the rats in various groups； Western blotting method was used to detect the expression levels of acyl-CoA synthetase long-chain family member 4 （ACSL4）， solute carrier family 7 member 11 （SLC7A11）， and glutathione peroxidase 4 （GPX4） proteins in the myocardium tissue of the rats in various groups. Additionally， H9c2 cardiomyocytes were divided into control group， SOR group， SOR+QSYQ group， and SOR+Fer-1 group. CCK-8 method was used to detect the survival rates of the cells in various groups； Western blotting method was used to detect the expression levels of ACSL4 and GPX4 proteins in the cells in various groups. Results Compared with control group， the level of CK-MB in serum of the rats in SOR group was significantly increased （P<0.05）， while the LVEF and LVFS were significantly decreased （P<0.05）； compared with SOR group， the levels of CK-MB in the serum of the rats in SOR+QSYQ group and SOR+Fer-1 group were significantly decreased （P<0.05）， while the LVEFs were significantly increased （P<0.05）. The HE staining results showed that compared with control group， the myocardial fibers of the rats in SOR group were disorderly arranged with enlarged intercellular spaces； compared with SOR group， the degrees of myocardial cell injury in SOR+QSYQ group and SOR+Fer-1 group were alleviated， and the myocardial fibers were arranged more neatly. The kit detection results showed that compared with control group， the levels of iron ion， MDA， and ROS in the myocardium tissue of the rats in SOR group were significantly increased （P<0.05）， while the level of GSH was significantly decreased （P<0.05）； compared with SOR group， the levels of iron ion and ROS in the myocardium tissue of the rats in SOR+QSYQ group and SOR+Fer-1 group were significantly decreased （P<0.05）， while the levels of GSH were significantly increased （P<0.05）. The Western blotting method results showed that compared with control group， the expression level of ACSL4 protein in the myocardium tissue of the rats in SOR group was significantly increased （P<0.05）， while the expression levels of SLC7A11 and GPX4 proteins were significantly decreased （P<0.05）； compared with SOR group， the expression levels of SLC7A11 and GPX4 proteins in the myocardium tissue of the rats in SOR+QSYQ group and SOR+Fer-1 group were significantly increased （P<0.05）， while the expression level of ACSL4 protein was significantly decreased （P<0.05）. The CCK-8 assay results showed that compared with 0 μmol·L^-1 SOR group， the survival rates of H9c2 cells treated with higher doses of SOR were significantly decreased （P<0.05）； compared with SOR group， the survival rates of the cells treated with different concentrations of QSYQ were significantly increased （P<0.05）， and the survival rate of the cells in 1 mg·L^-1 QSYQ intervention group was the highest. The Western blotting method results showed that compared with control group， the expression level of ACSL4 protein in the H9c2 cardiomyocytes in SOR group was significantly increased （P<0.05）， while the expression level of GPX4 protein was significantly decreased （P<0.05）； compared with SOR group， the expression levels of ACSL4 protein in the cells in SOR+QSYQ group and SOR+Fer-1 group were significantly decreased （P<0.05）， while the expression levels of GPX4 protein were significantly increased （P<0.05）. Conclusion ?QSYQ dropping pill can alleviate SOR-induced myocardial injury in the rats， and its mechanism may be related to the inhibition of ferroptosis in cardiomyocytes.

Key words: Qishen Yiqi dropping pill, Sorafenib, Ferroptosis, Myocardium injury, Oxidative stress

中图分类号:

R285.5

唐峥,刘薇,胡红民,赖琦,石妍,刘盛权,杨军,褚春. 芪参益气滴丸对索拉非尼诱导大鼠心肌损伤的改善作用及其机制[J]. 吉林大学学报(医学版), 2026, 52(2): 308-317.

Zheng TANG,Wei LIU,Hongmin HU,Qi LAI,Yan SHI,Shengquan LIU,Jun YANG,Chun CHU. Improvement effect of Qishen Yiqi dropping pills on myocardium injury in rats induced by sorafenib and its mechanism[J]. Journal of Jilin University(Medicine Edition), 2026, 52(2): 308-317.

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Group	n	CK-MB
Control	10	505.28±119.20
SOR	7	1 930.00±467.90^*
SOR+QSYQ	8	1 072.72±272.60^△
SOR+Fer-1	9	789.97±184.50^△

Group	LVEF（η/%）	LVFS（η/%）	Cardiac index [ω_B/（mg·g^-1）]
Control	85.40±3.58	49.80±4.66	2.65±0.18
SOR	74.00±4.85^*	38.00±4.30^*	3.04±0.50
SOR+QSYQ	82.80±5.93^△	46.80±7.29	2.90±0.14
SOR+Fer-1	84.40±4.51^△	47.00±6.36	2.86±0.60

Group	Fe²⁺ [m_B/（μmol·g^-1）]	MDA [m_B/（μmol·g^-1）]	GSH [m_B/（μmol·g^-1）]	ROS
Control	16.38±8.05	3.40±1.05	13.31±4.24	30.26±2.32
SOR	33.51±4.67^*	6.76±1.80^*	3.00±2.55^*	53.07±8.14^*
SOR+QSYQ	17.09±6.40^△	5.24±1.16	11.53±5.00^△	34.05±4.45^△
SOR+Fer-1	23.11±4.61^△	5.16±1.41	11.34±3.88^△	43.63±7.05^△

芪参益气滴丸对索拉非尼诱导大鼠心肌损伤的改善作用及其机制

Improvement effect of Qishen Yiqi dropping pills on myocardium injury in rats induced by sorafenib and its mechanism

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