中国临床药理学杂志

熊果苷调控Notch1/Hes1通路对缺氧/复氧诱导的心肌细胞损伤影响的研究

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陈红芬 , 吕孝欣 , 张玉清

中国临床药理学杂志 | 临床与基础桥接研究 2026,42(7): 947-953

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中国临床药理学杂志 |临床与基础桥接研究 2026 , 42 (7) : 947 -953

熊果苷调控Notch1/Hes1通路对缺氧/复氧诱导的心肌细胞损伤影响的研究

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陈红芬, 吕孝欣, 张玉清

作者信息

山东第二医科大学附属医院心血管内一科，山东潍坊 261031

通讯作者:

张玉清，副主任医师 MP: 13953604670 E-mail: udwchn@163.com

作者简介:

陈红芬（1977-），女，副主任医师，主要从事内科急危重症的救治工作和研究

The effect of arbutin on hypoxia/reoxygenation induced myocardial cell injury by modulating the Notch1/Hes1 pathway

Hong-fen CHEN, Xiao-xin LÜ, Yu-qing ZHANG

Affiliations

Department of Cardiovascular Internal Medicine, The Second Hospital of Shandong University, Weifang, 261031, Shandong Province, China

出版时间: 2026-04-17 doi: 10.13699/j.cnki.1001-6821.2026.07.008

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摘要

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目的

探讨熊果苷调控缺刻基因1（Notch1）/发状分裂相关增强子1（Hes1）通路对缺氧/复氧（H/R）诱导的心肌细胞（H9C2）损伤的影响。

方法

将H9C2细胞分为正常组、模型组、低、中、高剂量实验组（25.00、50.00、100.00 μmoL·L^-1的熊果苷）、抑制剂组｛100.00 μmoL·L^-1的熊果苷+10.00 μmoL·L^-1 N-[N-（3，5-二氟苯乙酰基）-L-丙氨酰]-S-苯基甘氨酸叔丁酯（DAPT）｝。正常组常规培养，其余各组均建立H/R诱导的H9C2细胞损伤模型，各给药组于造模前分别给予不同浓度熊果苷（12.50~200.00 μmoL·L^-1）预处理24 h。细胞计数（CCK-8）法与原位末端凋亡（TUNEL）分别检测细胞增殖与凋亡，JC-1法测线粒体膜电位，试剂盒检测活性氧（ROS）、乳酸脱氢酶（LDH）、谷胱甘肽过氧化物酶（GSH-Px）、丙二醛（MDA）、超氧化物歧化酶（SOD）水平，蛋白质印迹法检测Notch1、Hes1、凋亡相关B淋巴细胞瘤2（Bcl-2）、Bcl-2相关X蛋白（Bax）、半胱天冬氨酸蛋白酶3（caspase-3）蛋白表达。

结果

25.00~200.00 μmoL·L^-1的熊果苷能够显著增加H/R诱导的H9C2细胞存活率（P<0.05），选择25.00、50.00、100.00 μmoL·L^-1的熊果苷作为低、中、高剂量进行后续实验。正常组、模型组、高剂量实验组、抑制剂组的肌酸激酶-MB（CK-MB）水平分别为（2.45±0.39）、（8.72±0.82）、（3.56±0.42）和（5.48±0.57）U·mL^-1；心肌肌钙蛋白I（cTnI）水平分别为（22.58±2.23）、（68.34±5.96）、（30.12±3.26）和（49.62±5.15）ng·L^-1；LDH水平分别为（53.42±5.44）、（163.72±13.41）、（65.45±6.57）和（98.33±9.85）U·L^-1；ROS相对水平分别为1.01±0.12、3.34±0.35、1.46±0.18和2.24±0.23；SOD水平分别为（96.23±8.12）、（24.31±2.24）、（78.39±7.93）和（43.78±4.49）U·mg^-1；GSH-Px水平分别为（74.82±7.55）、（16.42±1.83）、（61.32±6.29）和（35.72±3.38）U·mg^-1；MDA水平分别为（15.45±2.03）、（58.33±5.57）、（21.56±2.24）和（42.47±4.13）μmol·L^-1；细胞凋亡率分别为（2.45±0.39）%、（29.86±3.25）%、（9.86±0.91）%和（21.34±2.25）%；红/绿荧光强度比值分别为（5.78±0.65）%、（1.42±0.20）%、（4.89±0.54）%和（2.85±0.33）%；Notch1蛋白表达分别为1.27±0.12、0.34±0.03、1.05±0.08和0.54±0.05；Hes1蛋白表达分别为0.95±0.10、0.25±0.03、0.81±0.08和0.57±0.05；Bcl-2蛋白表达分别为1.01±0.11、0.31±0.03、0.89±0.08和0.61±0.06；Bax蛋白表达分别为0.45±0.04、1.34±0.12、0.61±0.06和0.93±0.09；caspase-3蛋白表达分别为0.23±0.03、0.91±0.09、0.37±0.04和0.64±0.06；正常组与模型组比较、模型组与低、中、高剂量实验组比较、高剂量实验组与抑制剂组比较，上述指标在统计学上均有统计学意义（均P<0.05）。

结论

熊果苷通过激活Notch1/Hes1通路，抑制氧化应激，减轻H/R诱导的H9C2细胞损伤。

关键词

熊果苷 / 缺氧/复氧 / 缺刻基因1/发状分裂相关增强子1通路 / 心肌细胞损伤

Abstract

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Objective

To investigation the effect of arbutin on hypoxia/reoxygenation (H/R)-induced injury of cardiomyocytes (H9C2) through the neurogenic locus notch homolog protein 1(Notch1)/hairy and enhancer of split 1 (Hes1) signaling pathway.

Methods

An H/R-induced H9C2 cell injury model was established. The optimal intervention concentration of arbutin was screened by pretreating cells with various concentrations (12.50-200.00 μmol·L^-1). H9C2 cells were divided into a normal group, a model group, experimental-L, M, H groups (25.00, 50.00, and 100.00 μmol·L^-1 arbutin, respectively), and an inhibitor group {100.00 μmol·L^-1 arbutin+10.00 μmol·L^-1 N-[N-(3, 5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT)}. Cells in the normal group were cultured under normal conditions, while H/R models were established in the remaining groups. All treatment groups received arbutin pretreatment at concentrations ranging from 12.50 to 200.00 μmol·L^-1 for 24 hours before modeling. Cell proliferation was detected by the CCK-8 assay, and apoptosis was assessed by TUNEL assay; mitochondrial membrane potential was measured by JC-1; reactive oxygen species (ROS), lactate dehydrogenase (LDH), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), and superoxide dismutase (SOD) levels were detected using kits. Expression of Notch1, Hes1, Bcl-2, Bax, and caspase-3 was detected by Western blot.

Results

Arbutin at concentrations of 25.00–200.00 μmol·L^-1 significantly increased the survival rate of H/R-induced H9C2 cells (P<0.05). Arbutin at 25.00, 50.00, and 100.00 μmol·L^-1 was selected as the low, medium, and high doses for subsequent experiments. The creatine kinase isoenzyme MB (CK-MB) levels in the normal group, model group, experimental-H group, and inhibitor group were (2.45±0.39), (8.72±0.82), (3.56±0.42), and (5.48±0.57) U·mL^-1, respectively; the cTnI levels were (22.58±2.23), (68.34±5.96), (30.12±3.26), and (49.62±5.15) ng·L^-1, respectively; the LDH levels were (53.42±5.44), (163.72±13.41), (65.45±6.57), and (98.33±9.85) U·L^-1, respectively; the relative ROS levels were 1.01±0.12, 3.34±0.35, 1.46±0.18, and 2.24±0.23, respectively; the SOD levels were (96.23±8.12), (24.31±2.24), (78.39±7.93), and (43.78±4.49) U·mg^-1, respectively; the GSH-Px levels were (74.82±7.55), (16.42±1.83), (61.32±6.29), and (35.72±3.38) U·mg^-1, respectively; the MDA levels were (15.45±2.03), (58.33±5.57), (21.56±2.24), and (42.47±4.13) μmol·L^-1, respectively; the apoptosis rates were (2.45±0.39)%, (29.86±3.25)%, (9.86±0.91)%, and (21.34±2.25)%, respectively; the red/green fluorescence intensity ratios were (5.78±0.65)%, (1.42±0.20)%, (4.89±0.54)%, and (2.85±0.33)%, respectively; the Notch1 protein expression levels were 1.27±0.12, 0.34±0.03, 1.05±0.08, and 0.54±0.05, respectively; the Hes1 protein expression levels were 0.95±0.10, 0.25±0.03, 0.81±0.08, and 0.57±0.05, respectively; the Bcl-2 protein expression levels were 1.01±0.11, 0.31±0.03, 0.89±0.08, and 0.61±0.06, respectively; the Bax protein expression levels were 0.45±0.04, 1.34±0.12, 0.61±0.06, and 0.93±0.09, respectively; and the caspase-3 protein expression levels were 0.23±0.03, 0.91±0.09, 0.37±0.04, and 0.64±0.06, respectively. Comparisons between the normal group and the model group, between the model group and the experimental-L, M, H groups, and between the experimental-H group and the inhibitor group all showed statistically significant differences for the above indicators (all P<0.05).

Conclusion

Arbutin alleviates H/R-induced H9C2 cell injury by activating the Notch1/Hes1 pathway and inhibiting oxidative stress.

Key words

arbutin / hypoxia/reoxygenation / neurogenic locus notch homolog protein 1/hairy and enhancer of split 1 pathway / myocardial cell injury

引用本文

陈红芬, 吕孝欣, 张玉清. 熊果苷调控Notch1/Hes1通路对缺氧/复氧诱导的心肌细胞损伤影响的研究. 中国临床药理学杂志, 2026 , 42 (7) : 947 -953 . DOI: 10.13699/j.cnki.1001-6821.2026.07.008

Hong-fen CHEN, Xiao-xin LÜ, Yu-qing ZHANG. The effect of arbutin on hypoxia/reoxygenation induced myocardial cell injury by modulating the Notch1/Hes1 pathway[J]. Chinese Journal of Clinical Pharmacology, 2026 , 42 (7) : 947 -953 . DOI: 10.13699/j.cnki.1001-6821.2026.07.008

基金

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山东省重点研发计划基金资助项目(2023-YBSF-015)

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2026年第42卷第7期

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doi: 10.13699/j.cnki.1001-6821.2026.07.008

接收时间：2025-09-22
首发时间：2026-08-06
出版时间：2026-04-17

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收稿日期：2025-09-22

基金

山东省重点研发计划基金资助项目(2023-YBSF-015)

作者信息

山东第二医科大学附属医院心血管内一科，山东潍坊 261031

通讯作者:

张玉清，副主任医师 MP: 13953604670 E-mail: udwchn@163.com

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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
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