中国临床药理学杂志

阿巴西普基于Notch1/HIF-1α通路介导miR-16-5p对急性心肌梗死大鼠心功能的研究

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李银萍 ¹ , 徐清斌 ¹ , 张世昌 ¹ , 马萌雪 ¹ , 赵文丽 ²

中国临床药理学杂志 | 临床与基础桥接研究 2026,42(2): 204-210

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中国临床药理学杂志 |临床与基础桥接研究 2026 , 42 (2) : 204 -210

阿巴西普基于Notch1/HIF-1α通路介导miR-16-5p对急性心肌梗死大鼠心功能的研究

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李银萍¹, 徐清斌¹, 张世昌¹, 马萌雪¹, 赵文丽²

作者信息

^1.宁夏医科大学总医院心脑血管病医院心内科，宁夏银川 750004

^2.宁夏医科大学总医院心内科，宁夏银川 750001

通讯作者:

赵文丽，副主任医师 MP: 17395073626 E-mail: zhaowenli20120318@163.com

作者简介:

李银萍（1983-），女，主治医师，主要从事心血管疾病相关的临床工作和研究

Research of abasiximab-mediated miR-16-5p in rats with acute myocardial infarction based on the Notch1/HIF-1α signaling pathway

Yin-ping LI¹, Qing-bin XU¹, Shi-chang ZHANG¹, Meng-xue MA¹, Wen-li ZHAO²

Affiliations

^1.Department of Cardiology, Cardiovascular and Cerebrovascular Disease Hospital, Ningxia Medical University General Hospital, Yinchuan 750004, Ningxia Province, China

^2.Department of Cardiology, General Hospital of Ningxia Medical University, Yinchuan 750001, Ningxia Province, China

出版时间: 2026-01-28 doi: 10.13699/j.cnki.1001-6821.2026.02.009

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摘要

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目的

基于神经源性基因Notch同源蛋白1（Notch1）/缺氧诱导因子1亚基α（HIF-1α）信号通路，研究阿巴西普（ABT）介导微小核糖核酸-16-5p（miR-16-5p）对急性心肌梗死（AMI）大鼠的作用及其机制。

方法

用左冠状动脉前支结扎法建立AMI大鼠模型。将50只大鼠随机分为假手术组（开胸后不进行结扎）、模型组、实验组（ABT 5 mg·kg^-1）、miR-16-5p阴性实验组（尾静脉注射腺病毒包被的NC-mimic）和miR-16-5p阳性实验组（尾静脉注射腺病毒包被的miR-16-5p mimic），每组10只。用超声法检测各组大鼠的心功能指标；用荧光原位杂交法检测大鼠心肌组织中miR-16-5p相对表达水平；用酶联免疫吸附试验法检测各组大鼠血清乳酸脱氢酶、肌酸激酶含量、心肌组织中炎症因子及氧化应激因子水平；用免疫荧光法检测各组大鼠心肌组织中Notch1和HIF-1α蛋白表达。

结果

假手术组、模型组、实验组的左室射血分数（EF）分别为（64.72±6.15）%、（42.70±5.26）%和（59.51±6.61）%；miR-16-5p相对荧光强度分别为1.00±0.11、2.53±0.33和1.37±0.19；假手术组、模型组、实验组、miR-16-5p阴性实验组、miR-16-5p阳性实验组乳酸脱氢酶（LDH）分别为（154.64±27.48）、（347.14±48.67）、（173.42±28.45）、（179.75±29.83）和（336.47±41.35）IU·L^-1；肌酸激酶（CPK）分别为（161.37±29.14）、（425.43±52.34）、（201.67±31.23）、（197.74±30.48）和（413.46±49.78）IU·L^-1；心肌组织白介素-1β（IL-1β）分别为（35.48±6.93）、（129.64±19.51）、（52.52±8.48）、（51.62±7.32）和（118.42±19.51）pg·mg^-1 prot；心肌组织超氧化物歧化酶分别为（83.45±13.42）、（34.54±5.61）、（76.63±15.63）、（75.87±14.23）和（41.75±5.92）U·mg^-1 prot；Notch1相对荧光强度分别为1.00±0.16、1.86±0.22、1.36±0.19、1.29±0.25和1.71±0.28；HIF-1α相对荧光强度分别为1.00±0.13、2.41±0.37、1.64±0.24、1.57±0.29和2.10±0.38；假手术组与模型组相比、模型组与实验组相比、miR-16-5p阴性实验组与miR-16-5p阳性实验组相比，以上指标在统计学上差异均有统计学意义（P<0.01，P<0.001）。

结论

ABT可能通过介导miR-16-5p表达调控Notch1/HIF-1α信号通路来保护AMI大鼠心功能，改善其心肌组织病理损伤和纤维化，减轻氧化应激反应与炎症反应。

关键词

阿巴西普 / 急性心肌梗死 / 微小核糖核酸-16-5p / 神经源性基因Notch同源蛋白1 / 缺氧诱导因子1亚基α

Abstract

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Objective

To investigate the effects of abatacept (ABT)-mediated micro ribonucleic acid-16-5p (miR-16-5p) in rats with acute myocardial infarction (AMI) based on the neurogenic locus notch homolog protein 1 (Notch1)/hypoxia inducible factor 1α (HIF-1α) signaling pathway.

Methods

AMI rat model was established using the left anterior descending coronary artery ligation method. A total of 50 rats were randomly divided into the sham-operation group (thoracotomy without ligation), model group, experimental group (5 mg·kg^-1 ABT), Ad-scramble group (tail vein injection of adenovirus-coated NC-mimic) and Ad-miR-16-5p group (tail vein injection of adenovirus-coated miR-16-5p mimic), with 10 rats in each group. Cardiac function indicators in each group were detected by echocardiography. Fluorescence in situ hybridization was used to detect miR-16-5p relative expression levels in rat myocardial tissue. Enzyme-linked immunosorbent assay was used to detect serum lactate dehydrogenase and creatine phosphohykinase levels, as well as inflammatory factor and oxidative stress factor levels in myocardial tissue. Immunofluorescence was used to detect Notch1 and HIF-1α protein expression in rat myocardial tissue.

Results

The left ventricular ejection fractions (EF) in the sham-operation group, model group and experimental group were (64.72±6.15)%, (42.70±5.26)% and (59.51±6.61)%, respectively; the relative fluorescence intensities of miR-16-5p were 1.00±0.11, 2.53±0.33 and 1.37±0.19, respectively; the lactate dehydrogenase (LDH) levels in the sham-operation group, model group, experimental group, Ad-scramble group and Ad-miR-16-5p group were (154.64±27.48), (347.14±48.67), (173.42±28.45), (179.75±29.83) and (336.47±41.35) IU·L^-1, respectively; the creatine phosphohykinase (CPK) levels were (161.37±29.14), (425.43±52.34), (201.67±31.23), (197.74±30.48) and (413.46±49.78) IU·L^-1, respectively; the interleukin-1β (IL-1β) levels in myocardial tissue were (35.48±6.93), (129.64±19.51), (52.52±8.48), (51.62±7.32) and (118.42±19.51) pg·mg^-1 prot, respectively; the superoxide dismutase levels in myocardial tissue were (83.45±13.42), (34.54±5.61), (76.63±15.63), (75.87±14.23) and (41.75±5.92) U·mg^-1 prot, respectively; the relative fluorescence intensities of Notch1 were 1.00±0.16, 1.86±0.22, 1.36±0.19, 1.29±0.25 and 1.71±0.28, respectively; the relative fluorescence intensities of HIF-1α were 1.00±0.13, 2.41±0.37, 1.64±0.24, 1.57±0.29 and 2.10±0.38, respectively; the above indicators showed statistically significant differences between the sham-operation group and the model group, between the model group and the experimental group, and between the Ad-scramble group and the Ad-miR-16-5p group (P<0.01, P<0.001).

Conclusion

ABT may protect cardiac function in AMI rats, improve myocardial tissue pathological damage and fibrosis, and reduce oxidative stress and inflammatory responses by mediating miR-16-5p expression to regulate the Notch1/HIF-1α signaling pathway.

Key words

abatacept / acute myocardial infarction / micro ribonucleic acid-16-5p / neurogenic locus notch homolog protein1 / hypoxia inducible factor1α

引用本文

李银萍, 徐清斌, 张世昌, 马萌雪, 赵文丽. 阿巴西普基于Notch1/HIF-1α通路介导miR-16-5p对急性心肌梗死大鼠心功能的研究. 中国临床药理学杂志, 2026 , 42 (2) : 204 -210 . DOI: 10.13699/j.cnki.1001-6821.2026.02.009

Yin-ping LI, Qing-bin XU, Shi-chang ZHANG, Meng-xue MA, Wen-li ZHAO. Research of abasiximab-mediated miR-16-5p in rats with acute myocardial infarction based on the Notch1/HIF-1α signaling pathway[J]. Chinese Journal of Clinical Pharmacology, 2026 , 42 (2) : 204 -210 . DOI: 10.13699/j.cnki.1001-6821.2026.02.009

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2026年第42卷第2期

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文章信息

doi: 10.13699/j.cnki.1001-6821.2026.02.009

接收时间：2025-05-08
首发时间：2026-08-06
出版时间：2026-01-28

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收稿日期：2025-05-08

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作者信息

^1.宁夏医科大学总医院心脑血管病医院心内科，宁夏银川 750004

^2.宁夏医科大学总医院心内科，宁夏银川 750001

通讯作者:

赵文丽，副主任医师 MP: 17395073626 E-mail: zhaowenli20120318@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
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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