中国临床药理学杂志

普拉格雷介导大鼠心肌细胞焦亡减轻心肌缺血再灌注氧化应激损伤的研究

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李华伟 ^1a , 张丽 ^1a , 王计亮 ^1a , 沈青青 ^1b , 刘黎洁 ^1a

中国临床药理学杂志 | 临床与基础桥接研究 2025,41(8): 1096-1101

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中国临床药理学杂志 |临床与基础桥接研究 2025 , 41 (8) : 1096 -1101

普拉格雷介导大鼠心肌细胞焦亡减轻心肌缺血再灌注氧化应激损伤的研究

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李华伟^1a, 张丽^1a, 王计亮^1a, 沈青青^1b, 刘黎洁^1a

作者信息

^1a.邢台市中心医院，心内科，河北邢台 054000

^1b.邢台市中心医院，心脏康复科，河北邢台 054000

通讯作者:

李华伟 MP: 15833381688 E-mail: 450779415@qq.com

作者简介:

李华伟（1989-），男，主治医师，主要从事冠心病的介入治疗和心脏康复医学方面的工作

Research on the reduction of myocardial ischemia-reperfusion oxidative stress injury in rats mediated by prasugrel

Hua-wei LI^1a, Li ZHANG^1a, Ji-liang WANG^1a, Qing-qing SHEN^1b, Li-jie LIU^1a

Affiliations

^1a.Department of Cardiology, Xingtai Central Hospital, Xingtai 054000, Hebei Province, China

^1b.Department of Cardiac Rehabilitation, Xingtai Central Hospital, Xingtai 054000, Hebei Province, China

出版时间: 2025-04-28 doi: 10.13699/j.cnki.1001-6821.2025.08.009

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摘要

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目的

探讨普拉格雷（PRAS）基于核因子E2相关因子2（Nrf2）/血红素加氧酶1（HO-1）/醌氧化还原酶1（NQO1）信号通路介导大鼠心肌细胞焦亡减轻心肌缺血再灌注（IR）氧化应激损伤的作用机制。

方法

将SD大鼠随机分为假手术组（仅暴露心脏，不构建IR模型，灌胃等量0.9% NaCl）、模型组（构建IR大鼠模型，灌胃等量0.9% NaCl）、低剂量实验组（模型组大鼠灌胃5 mg·kg^-1 PRAS）、中剂量实验组（模型组大鼠灌胃10 mg·kg^-1 PRAS）、高剂量实验组（模型组大鼠灌胃15 mg·kg^-1 PRAS）。用酶联免疫吸附试验法检测大鼠血清中心肌损伤标志物和氧化应激因子水平，用蛋白质印迹法检测各组大鼠心肌组织中细胞焦亡相关蛋白和Nrf2/HO-1/NQO1信号通路相关蛋白的相对表达水平。

结果

假手术组、模型组和低、中、高剂量实验组的心肌肌钙蛋白（cTnⅠ）含量分别为（264.52±39.04）、（558.40±101.68）、（477.65±64.33）、（429.71±75.94）和（313.84±52.26）pg·mL^-1，肌酸激酶同工酶（CK-MB）含量分别为（0.68±0.11）、（2.76±0.45）、（1.92±0.27）、（1.53±0.23）和（1.11±0.19）U·L^-1，丙二醛（MDA）水平分别为（4.05±0.68）、（10.12±1.74）、（8.44±1.26）、（6.79±1.05）和（5.47±1.02）nmol·L^-1，核苷酸结合寡聚化结构域样受体蛋白3（NLRP3）蛋白相对表达水平分别为1.00±0.14、2.16±0.32、1.72±0.25、1.54±0.28和1.28±0.21，Nrf2蛋白相对表达水平分别为1.00±0.15、0.32±0.04、0.39±0.05、0.61±0.10和0.80±0.13，模型组的上述指标与假手术组比较，低、中、高剂量实验组的上述指标与模型组比较，均有显著性差异（P<0.05，P<0.01，P<0.001）。

结论

PRAS可能通过激活Nrf2/HO-1/NQO1信号通路抵抗氧化应激，减少心肌细胞的焦亡和凋亡，从而减轻IR损伤，保护心脏功能。

关键词

普拉格雷 / 心肌缺血再灌注 / 细胞焦亡 / 氧化应激损伤 / 核因子E2相关因子2/血红素加氧酶1/醌氧化还原酶1信号通路

Abstract

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Objective

To explore the mechanism of prasugrel (PRAS) in alleviating oxidative stress of myocardial ischemia reperfusion (IR) by inducing pyroptosis of rat cardiomyocytes based on nuclear factor erythroid derived 2-like 2 (Nrf2)/heme oxygenase-1 (HO-1)/NAD(P)H quinone oxidoreductase 1 (NQO1) signaling pathway.

Methods

SD rats were randomly divided into sham operation group (only the heart was exposed, no IR model was constructed, and the same amount of normal saline was injected into the stomach), model group (IR rat model was constructed, and the stomach was given an equal amount of 0.9% NaCl), the experimental-L group (model group rats were intragastric with 5 mg·kg^-1 PRAS), the experimental-M group (model group rats were intragastric with 10 mg·kg^-1 PRAS), and experimental-H group (model group rats were intragastric with 15 mg·kg^-1 PRAS). The serum levels of myocardial injury markers and oxidative stress factors were detected by enzyme-linked immunosorbent assay. The relative expression levels of pyroptosis-related proteins and Nrf2/HO-1/NQO1 signaling pathway-related proteins in myocardial tissue were detected by Western blot.

Results

The contents of cardiac troponin Ⅰ (cTnⅠ) in sham operation group, model group, experimental-L group, experimental-M group and experimental-H group were (264.52±39.04), (558.40±101.68), (477.65±64.33), (429.71±75.94) and (313.84±52.26) pg·mL^-1, respectively; the creatine kinase isoenzyme (CK-MB) levels were (0.68±0.11), (2.76±0.45), (1.92±0.27), (1.53±0.23) and (1.11±0.19) U·L^-1, respectively; the levels of malondialdehyde (MDA) were (4.05±0.68), (10.12±1.74), (8.44±1.26), (6.79±1.05) and (5.47±1.02) nmol·L^-1, respectively; the relative expression levels of nucleotide binding oligomerization domain-like receptor protein 3 (NLRP3) were 1.00±0.14, 2.16±0.32, 1.72±0.25, 1.54±0.28 and 1.28±0.21, respectively; the relative expression levels of Nrf2 were 1.00±0.15, 0.32±0.04, 0.39±0.05, 0.61±0.10 and 0.80±0.13, respectively. The above indexes of model group were compared with those of sham-operation group, and those of experimental-L, experimental-M and experimental-H groups were compared with those of model group (P<0.05, P<0.01, P<0.001).

Conclusion

PRAS may resist oxidative stress and reduce pyroptosis and apoptosis of myocardial cells by activating Nrf2/HO-1/NQO1 signaling pathway, thereby alleviating IR injury and protecting cardiac function.

Key words

prasugrel / myocardial ischemia-reperfusion / pyroptosis / oxidative stress injury / nuclear factor erythroid derived 2-like 2/heme oxygenase-1/NAD(P)H quinone dehydrogenase 1 signal pathway

引用本文

李华伟, 张丽, 王计亮, 沈青青, 刘黎洁. 普拉格雷介导大鼠心肌细胞焦亡减轻心肌缺血再灌注氧化应激损伤的研究. 中国临床药理学杂志, 2025 , 41 (8) : 1096 -1101 . DOI: 10.13699/j.cnki.1001-6821.2025.08.009

Hua-wei LI, Li ZHANG, Ji-liang WANG, Qing-qing SHEN, Li-jie LIU. Research on the reduction of myocardial ischemia-reperfusion oxidative stress injury in rats mediated by prasugrel[J]. Chinese Journal of Clinical Pharmacology, 2025 , 41 (8) : 1096 -1101 . DOI: 10.13699/j.cnki.1001-6821.2025.08.009

基金

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邢台市重点研发计划基金资助项目(2022ZC117)

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2025年第41卷第8期

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文章信息

doi: 10.13699/j.cnki.1001-6821.2025.08.009

接收时间：2024-10-21
首发时间：2026-08-04
出版时间：2025-04-28

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收稿日期：2024-10-21

基金

邢台市重点研发计划基金资助项目(2022ZC117)

作者信息

^1a.邢台市中心医院，心内科，河北邢台 054000

^1b.邢台市中心医院，心脏康复科，河北邢台 054000

通讯作者:

李华伟 MP: 15833381688 E-mail: 450779415@qq.com

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https://castjournals.cast.org.cn/joweb/zglcylxzz/CN/10.13699/j.cnki.1001-6821.2025.08.009

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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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