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

Abstract

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

CLC Number:

R285.5

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.

Figures/Tables 9

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References 29

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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^△

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

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