中国临床药理学杂志

瑞芬太尼后处理减轻心肌缺血再灌注后炎症反应和细胞凋亡及其机制研究

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陈中青 ^1a , 侯丹丹 ^1b , 王晨晨 ^1b

中国临床药理学杂志 | 临床与基础桥接研究 2026,42(7): 975-981

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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) : 975 -981

瑞芬太尼后处理减轻心肌缺血再灌注后炎症反应和细胞凋亡及其机制研究

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陈中青^1a, 侯丹丹^1b, 王晨晨^1b

作者信息

^1a.宁夏医科大学总医院，老年与特需医学科，宁夏回族自治区银川 750004

^1b.宁夏医科大学总医院，心脏中心内科，宁夏回族自治区银川 750004

通讯作者:

陈中青，硕士生导师 MP: 13895078589 E-mail: czq6699@sina.com

作者简介:

陈中青（1973-），女，主任医师，主要从事冠心病心肌保护方面的工作和研究

Remifentanil post-treatment against myocardial ischemia-reperfusion injury by attenuating inflammatory and apoptosis in rats and its mechanism

Zhong-qing CHEN^1a, Dan-dan HOU^1b, Chen-chen WANG^1b

Affiliations

^1a.Department of Geriatrics and Special Needs Medicine, General Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China

^1b.Heart Centre, Department of Cardiovascular, General Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China

出版时间: 2026-04-17 doi: 10.13699/j.cnki.1001-6821.2026.07.012

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摘要

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目的

探讨磷脂酰肌醇3-激酶-蛋白激酶B-核因子E2相关因子2（PI3K-Akt-Nrf2）通路在瑞芬太尼后处理保护大鼠心肌缺血再灌注（IR）损伤中的作用。

方法

用冠状动脉前降支结扎法，建立SD大鼠心肌缺血再灌注损伤的模型。将成年雄性SD大鼠随机分为对照组（只穿线不结扎）、模型组（心肌缺血30 min后再灌注30 min）、实验组（从大鼠缺血25 min至再灌注前5 min内，连续输注瑞芬太尼10 μg·kg^-1·min^-1）、LY294002组（给予瑞芬太尼干预的同时给予0.3 mg·kg^-1 LY294002）及ML385组（给予瑞芬太尼干预的同时给予30 mg·kg^-1 ML385）。用酶联免疫吸附实验（ELISA）检测血清白介素6（IL-6）、IL-1β、肿瘤坏死因子α（TNF-α）浓度；采用原末端转移酶标记法（TUNEL）检测凋亡指数（AI）；实时荧光定量聚合酶链反应检测PI3K、Akt的表达水平。

结果

对照组、模型组、实验组、LY294002组和ML385组的IL-6水平分别为0.76±0.15、3.44±0.35、1.46±0.37、3.17±0.28和3.07±0.18，IL-1β水平分别为0.34±0.08、1.18±0.21、0.66±0.28、0.94±0.13和0.81±0.25，TNF-α水平分别为0.98±0.17、2.38±0.27、1.17±0.21、2.27±0.26和2.66±0.16，AI水平分别为0.95±0.67、20.73±1.63、10.20±2.48、15.69±2.41和16.31±1.55，PI3K mRNA相对表达水平分别为1.00±0.08、1.69±0.15、1.90±0.12、0.98±0.14和1.78±0.13，Akt mRNA相对表达水平分别为1.00±0.09、1.56±0.22、1.85±0.13、0.87±0.21和1.69±0.31，Nrf2 mRNA相对表达水平分别为1.00±0.08、2.62±0.16、3.11±0.28、1.37±0.25和1.03±0.14。实验组上述指标与模型组比较，LY294002组及ML385组上述指标与实验组比较，在统计学上差异均有统计学意义（P<0.05，P<0.01，P<0.001，P<0.0001）。

结论

瑞芬太尼后处理通过减少IR诱导的大鼠心肌细胞凋亡和炎症反应发挥对心肌IR损伤的保护作用，并可能与PI3K/Akt/Nrf2信号通路有关。

关键词

瑞芬太尼 / 心肌缺血再灌注损伤 / 磷脂酰肌醇3-激酶/蛋白激酶B/核因子E2相关因子2通路 / 细胞凋亡 / 炎症

Abstract

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Objective

To investigate the role of the phosphatidyqinositol-3 kinase / protein kinase B / nuclear factor-erythroid 2 related factor 2 (PI3K/Akt/Nrf2) pathway in remifentanil postconditioning-induced protection against myocardial ischemia-reperfusion (IR) injury in rats.

Methods

Establishing a rat model of myocardial ischemia-reperfusion injury (MIRI) by left anterior descending coronary artery ligation. Subsequently, the rats were randomly assigned to the following groups: control (only threading was performed without ligation), model (ischemia was induced for 30 minutes followed by 30 minutes of reperfusion), experimental (remifentanil was continuously infused by at a dose of 10 μg·kg^-1·min^-1 from 25 minutes of ischemia to 5 minutes before reperfusion), LY294002 (while receiving remifentanil intervention, 0.3 mg·kg^-1 LY294002 was administered), and ML385 (while receiving remifentanil intervention, 30 mg·kg^-1 ML385 was administered). Serum levels of interleukin-6 (IL-6), IL-1β and tumor necrosis factor-alpha (TNF-α) were measured using enzyme-linked immunosorbent assay (ELISA). Apoptosis index (AI) of myocardial cells in each group was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). The expression levels of phosphatidylinositol 3-kinase (PI3K) and protein kinase B (Akt) were measured using real-time quantitative polymerase chain reaction.

Results

The measured parameters for the control, model, experimental, LY294002, and ML385 groups were as follows. Serum interleukin-6 (IL-6) were 0.76±0.15, 3.44±0.35, 1.46±0.37, 3.17±0.28 and 3.07±0.18. IL-1β were 0.34±0.08, 1.18±0.21, 0.66±0.28, 0.94±0.13 and 0.81±0.25, respectively. Serum tumor necrosis factor-α (TNF-α) were 0.98±0.17, 2.38±0.27, 1.17±0.21, 2.27±0.26 and 2.66±0.16, respectively. Apoptosis index (AI) were 0.95±0.67, 20.73±1.63, 10.20±2.48, 15.69±2.41 and 16.31±1.55, respectively. PI3K mRNA relative expression level were 1.00±0.08, 1.69±0.15, 1.90±0.12, 0.98±0.14 and 1.78±0.13, respectively. Akt mRNA relative expression level were 1.00±0.09, 1.56±0.22, 1.85±0.13, 0.87±0.21 and 1.69±0.31, respectively. Nrf2 mRNA relative expression level were 1.00±0.08, 2.62±0.16, 3.11±0.28, 1.37±0.25 and 1.03±0.14, respectively. Statistically significant differences were observed for all the above parameters when comparing the experimental group with the model group, and when comparing the LY294002 and ML385 groups with the experimental group (P<0.05, P<0.01, P<0.001, P<0.0001).

Conclusion

Remifentanil postconditioning exerts a protective effect on myocardial IR injury by reducing IR-induced cardiomyocyte apoptosis and inflammatory response in rats, and may be related to the PI3K / Akt / Nrf2 signaling pathway.

Key words

remifentanil / myocardial ischemia-reperfusion injury / phosphatidylinositol 3-kinase / protein kinase B / nuclear factor erythroid 2-related factor 2 pathway / apoptosis / inflammatory

引用本文

陈中青, 侯丹丹, 王晨晨. 瑞芬太尼后处理减轻心肌缺血再灌注后炎症反应和细胞凋亡及其机制研究. 中国临床药理学杂志, 2026 , 42 (7) : 975 -981 . DOI: 10.13699/j.cnki.1001-6821.2026.07.012

Zhong-qing CHEN, Dan-dan HOU, Chen-chen WANG. Remifentanil post-treatment against myocardial ischemia-reperfusion injury by attenuating inflammatory and apoptosis in rats and its mechanism[J]. Chinese Journal of Clinical Pharmacology, 2026 , 42 (7) : 975 -981 . DOI: 10.13699/j.cnki.1001-6821.2026.07.012

基金

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宁夏自然科学基金资助项目(2024AAC03676)

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2026年第42卷第7期

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文章信息

doi: 10.13699/j.cnki.1001-6821.2026.07.012

接收时间：2026-01-06
首发时间：2026-08-06
出版时间：2026-04-17

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收稿日期：2026-01-06

基金

宁夏自然科学基金资助项目(2024AAC03676)

作者信息

^1a.宁夏医科大学总医院，老年与特需医学科，宁夏回族自治区银川 750004

^1b.宁夏医科大学总医院，心脏中心内科，宁夏回族自治区银川 750004

通讯作者:

陈中青，硕士生导师 MP: 13895078589 E-mail: czq6699@sina.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
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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