中国临床药理学杂志

野马追内酯B通过p38 MAPK调控阿霉素诱导心肌病中心肌细胞凋亡及炎症的研究

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陈徐波 ^1a^,²^,³ , 黄春艳 ^1a^,²^,³ , 胡益冰 ^1b^,²^,³ , 许竞 ⁴ , 潘轶斌 ^1a^,²^,³^,⁵

中国临床药理学杂志 | 临床与基础桥接研究 2026,42(9): 1293-1300

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中国临床药理学杂志 |临床与基础桥接研究 2026 , 42 (9) : 1293 -1300

野马追内酯B通过p38 MAPK调控阿霉素诱导心肌病中心肌细胞凋亡及炎症的研究

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陈徐波^1a^,²^,³, 黄春艳^1a^,²^,³, 胡益冰^1b^,²^,³, 许竞⁴, 潘轶斌^1a^,²^,³^,⁵

作者信息

^1a.金华市中心医院/浙江大学医学院附属金华医院心血管内科，浙江金华 321000

^1b.金华市中心医院/浙江大学医学院附属金华医院消化内科，浙江金华 321000

^2.金华市心血管介入质控中心，浙江金华 321000

^3.中国医学科学院阜外医院心血管病技术培训中心，浙江金华 321000

^4.温州医科大学第二临床医学院，浙江温州 325000

^5.浙江大学医学院，浙江杭州 310058

通讯作者:

潘轶斌，主任医师，硕士生导师 MP: 13868982160 E-mail: pyb202208@163.com

作者简介:

陈徐波（1991-），男，主治医师，主要从事心血管疾病的研究

Research of eupalinolide B regulating cardiomyocyte apoptosis and inflammation in doxorubicin-induced cardiomyopathy through p38 MAPK

Xu-bo CHEN^1a^,²^,³, Chun-yan HUANG^1a^,²^,³, Yi-bing HU^1b^,²^,³, Jing XU⁴, Yi-bin PAN^1a^,²^,³^,⁵

Affiliations

^1a.Department of Cardiovascular Internal Medicine, Jinhua Municipal Central Hospital/Jinhua Hospital Affiliated to Zhejiang University School of Medicine, Jinhua 321000, Zhejiang Province, China

^1b.Department of Digestive Medicine, Jinhua Municipal Central Hospital/Jinhua Hospital Affiliated to Zhejiang University School of Medicine, Jinhua 321000, Zhejiang Province, China

^2.Jinhua Cardiovascular Interventional Quality Control Center, Jinhua 321000, Zhejiang Province, China

^3.Cardiovascular Technology Training Center, Fuwai Hospital, Chinese Academy of Medical Sciences, Jinhua 321000, Zhejiang Province, China

^4.College of Second Clinical Medical, Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China

^5.College of Medicine, Zhejiang University, Hangzhou 310058, Zhejiang Province, China

出版时间: 2026-05-17 doi: 10.13699/j.cnki.1001-6821.2026.09.015

文章导航

摘要

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目的

探讨野马追内酯B（EB）在阿霉素（DOX）诱导扩张型心肌病（DCM）的潜在靶点及通路，并验证EB是否通过调控p38丝裂原活化蛋白激酶（p38 MAPK）信号通路抑制心肌细胞凋亡及炎症反应。

方法

用数据库筛选EB与DCM的交集靶点，进行功能与通路富集分析及分子对接验证。构建DCM小鼠模型，建模成功后的小鼠随机分为模型组、低剂量实验组（5 mg·kg^-1 EB）、高剂量实验组（20 mg·kg^-1 EB）、阳性对照组（5 mg·kg^-1阳性药物卡托普利captopril）、抑制剂组（1 mg·kg^-1 p38 MAPK抑制剂SB203580）和激活剂组（20 mg·kg^-1 EB+0.10 mg·kg^-1 p38 MAPK激活剂anisomycin），另外选取正常健康小鼠为空白组（给予等剂量生理盐水）。每组10只。给药干预结束后，用超声心电图法检测各组小鼠心功能；收集血清和心肌组织，用酶联免疫吸附测定法（ELISA）检测血清炎症因子及心肌损伤标志物水平变化；用苏木精-伊红（HE）、马松（Masson）和末端脱氧核苷酸转移酶介导的dUTP缺口末端标记（TUNEL）染色法检测心肌组织病理损伤、纤维化及细胞凋亡变化；用免疫组化法和蛋白质印迹法检测心肌组织中凋亡、炎症因子、磷酸化（p-）p38 MAPK和p38 MAPK蛋白表达情况。

结果

共筛选出EB存在34个潜在作用靶点，DCM特异性靶点1 018个，EB治疗DCM潜在作用靶点5个，涉及MAPK信号通路等。空白组、模型组、低剂量实验组、高剂量实验组、抑制剂组和激活剂组的左室短轴缩短率（LVFS）分别为（41.26±0.07）%、（26.60±0.72）%、（30.90±0.29）%、（44.26±1.73）%、（42.62±1.82）%和（33.66±2.74）%；N末端B型利钠肽原（NT-proBNP）分别为（734.85±90.24）、（1 509.28±163.17）、（1 240.62±157.95）、（841.57±88.06）、（862.91±87.92）和（1 159.76±125.71）pg·mL^-1；B细胞淋巴瘤因子-2（Bcl-2）阳性率分别为（16.81±1.82）%、（3.02±0.54）%、（6.97±0.86）%、（14.29±1.43）%、（13.51±1.46）%和（8.14±0.95）%；Bcl-2相关X蛋白（Bax）阳性率分别为（1.59±0.18）%、（18.37±2.51）%、（12.42±1.63）%、（3.84±0.45）%、（4.09±0.41）%和（11.53±1.28）%；p-p38 MAPK/p38 MAPK相对表达水平分别为0.23±0.03、0.86±0.09、0.64±0.08、0.35±0.04、0.38±0.05和0.61±0.08，模型组与空白组比较，低、高剂量实验组和抑制剂组与模型组比较，激活剂组与高剂量实验组比较，上述指标在统计学上差异均有统计学意义（均P<0.05）。

结论

EB可能通过抑制p38 MAPK磷酸化，减轻DOX诱导的心肌病小鼠心肌炎症反应和心肌细胞凋亡，改善心肌损伤。

关键词

野马追内酯B / 心肌病 / p38丝裂原活化蛋白激酶 / 凋亡 / 炎症

Abstract

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Objective

To investigate the potential targets and pathways of eupalinolide B (EB) in doxorubicin (DOX)-induced dilated cardiomyopathy (DCM), and to verify EB inhibits cardiomyocyte apoptosis and inflammatory response by regulating the p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway.

Methods

Database screening was used to identify the intersecting targets of EB and DCM, followed by functional and pathway enrichment analyses and molecular docking validation. A DCM mouse model was established. The successfully modeled mice were randomly divided into model group, experimental-L group (5 mg·kg^-1 EB), experimental-H group (20 mg·kg^-1 EB), positive control group (5 mg·kg^-1 positive drug captopril), inhibitor group (1 mg·kg^-1 p38 MAPK inhibitor SB203580) and activator group (20 mg·kg^-1 EB+0.10 mg·kg^-1 p38 MAPK activator anisomycin). In addition, normal and healthy mice were selected as the blank group. Each group had 10 mice. After the intervention, cardiac function was detected by echocardiography; serum and myocardial tissues were collected, serum inflammatory factors and myocardial injury markers were measured by enzyme-linked immunosorbent assay (ELISA); pathological damage, fibrosis and cell apoptosis of myocardial tissue were detected by hematoxylin and eosin (HE) staining, Masson staining and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining; the expression of apoptosis-related proteins, inflammatory factors, phosphorylation (p-)p38 MAPK and p38 MAPK in myocardial tissue was detected by immunohistochemistry and Western blot.

Results

A total of 34 potential targets of EB and 1 018 DCM-specific targets were screened, and 5 potential targets of EB for DCM treatment were identified, involving the MAPK signaling pathway. The left ventricular fractional shortening (LVFS) values in blank group, model group, experimental-L group, experimental-H group, inhibitor group and activator group were (41.26±0.07)%, (26.60±0.72)%, (30.90±0.29)%, (44.26±1.73)%, (42.62±1.82)% and (33.66±2.74)%, respectively; the N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were (734.85±90.24), (1 509.28±163.17), (1 240.62±157.95), (841.57±88.06), (862.91±87.92) and (1 159.76±125.71) pg·mL^-1, respectively; the B-cell lymphoma-2 (Bcl-2) positive rates were (16.81±1.82)%, (3.02±0.54)%, (6.97±0.86)%, (14.29±1.43)%, (13.51±1.46)% and (8.14±0.95)%, respectively; the Bcl-2-associated X protein (Bax) positive rates were (1.59±0.18)%, (18.37±2.51)%, (12.42±1.63)%, (3.84±0.45)%, (4.09±0.41)% and (11.53±1.28)%, respectively; the relative expression levels of p-p38 MAPK/p38 MAPK were 0.23±0.03, 0.86±0.09, 0.64±0.08, 0.35±0.04, 0.38±0.05 and 0.61±0.08, respectively. Comparisons between model group and blank group, between experimental-L/-H groups or inhibitor group and model group, and between activator groups and experimental-H group, the above indicators all showed statistically significant differences (all P<0.05).

Conclusion

EB may alleviate the myocardial inflammatory response and cardiomyocyte apoptosis in DOX-induced cardiomyopathy mice and improve myocardial damage by inhibiting the phosphorylation of p38 MAPK.

Key words

eupalinolide B / p38 mitogen-activated protein kinase / cardiomyopathy / apoptosis / inflammation

引用本文

陈徐波, 黄春艳, 胡益冰, 许竞, 潘轶斌. 野马追内酯B通过p38 MAPK调控阿霉素诱导心肌病中心肌细胞凋亡及炎症的研究. 中国临床药理学杂志, 2026 , 42 (9) : 1293 -1300 . DOI: 10.13699/j.cnki.1001-6821.2026.09.015

Xu-bo CHEN, Chun-yan HUANG, Yi-bing HU, Jing XU, Yi-bin PAN. Research of eupalinolide B regulating cardiomyocyte apoptosis and inflammation in doxorubicin-induced cardiomyopathy through p38 MAPK[J]. Chinese Journal of Clinical Pharmacology, 2026 , 42 (9) : 1293 -1300 . DOI: 10.13699/j.cnki.1001-6821.2026.09.015

基金

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浙江省医药卫生科技计划基金资助项目(2019RC302)
金华市科技计划基金资助项目(2023-3-107)

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2026年第42卷第9期

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文章信息

doi: 10.13699/j.cnki.1001-6821.2026.09.015

接收时间：2026-04-20
首发时间：2026-08-06
出版时间：2026-05-17

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收稿日期：2026-04-20

基金

浙江省医药卫生科技计划基金资助项目(2019RC302)

金华市科技计划基金资助项目(2023-3-107)

作者信息

^1a.金华市中心医院/浙江大学医学院附属金华医院心血管内科，浙江金华 321000

^1b.金华市中心医院/浙江大学医学院附属金华医院消化内科，浙江金华 321000

^2.金华市心血管介入质控中心，浙江金华 321000

^3.中国医学科学院阜外医院心血管病技术培训中心，浙江金华 321000

^4.温州医科大学第二临床医学院，浙江温州 325000

^5.浙江大学医学院，浙江杭州 310058

通讯作者:

潘轶斌，主任医师，硕士生导师 MP: 13868982160 E-mail: pyb202208@163.com

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https://castjournals.cast.org.cn/joweb/zglcylxzz/CN/10.13699/j.cnki.1001-6821.2026.09.015

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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