[1]霍嘉琪,袁明杰,田厚泽,等.白细胞介素-21通过si-信号转导和转录活化因子3促进小鼠心肌梗死后血管生成并抑制心脏重构[J].陕西医学杂志,2025,54(1):44-51.[doi:DOI:10.3969/j.issn.1000-7377.2025.01.008]
　HUO Jiaqi,YUAN Mingjie,TIAN Houze,et al.Interleukin-21 enhances angiogenesis and inhibits myocardial remodeling after myocardial infarction through targeting STAT3[J].,2025,54(1):44-51.[doi:DOI:10.3969/j.issn.1000-7377.2025.01.008]
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白细胞介素-21通过si-信号转导和转录活化因子3促进小鼠心肌梗死后血管生成并抑制心脏重构
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《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
54
期数:
2025年1期
页码:
44-51
栏目:
基础研究
出版日期:
2025-01-05

文章信息/Info

Title:
Interleukin-21 enhances angiogenesis and inhibits myocardial remodeling after myocardial infarction through targeting STAT3
作者:
霍嘉琪1; 袁明杰1; 田厚泽2; 幸世峰1
(1.新疆医科大学第五附属医院心内科, 新疆 乌鲁木齐 830011; 2.新疆医科大学第二附属医院脊柱外科, 新疆 乌鲁木齐 830063)
Author(s):
HUO Jiaqi; YUAN Mingjie; TIAN Houze; XING Shifeng
(Department of Cardiovascular Medicine,The Fifth Affiliated Hospital of Xinjiang Medical University,Urumqi 830011,China)
关键词:
心肌梗死;  白细胞介素-21;  血管生成;  信号转导和转录活化因子3;  心脏重构;  炎症;  凋亡
Keywords:
Myocardial infarction;  Interleukin-21;  Angiogenesis;  Signal transducer and activator of transcription 3;  Cardiac remodeling;  Inflammation;  Apoptosis
分类号:
R 541.4
DOI:
DOI:10.3969/j.issn.1000-7377.2025.01.008
文献标志码:
A
摘要:
目的:探讨白细胞介素(IL)-21对心肌梗死(MI)小鼠毛细血管生成和心脏重构的影响及其潜在的分子机制。方法:60只大鼠分为假手术组、MI组、MI+IL-21组,每组20只。建立MI模型,超声心动图测量左室收缩末期内径(LVESD)、舒张末期内径(LVEDD)、心脏左室射血分数(LVEF),计算左室短轴缩短率(FS),2,3,5-三苯基氯化四氮唑溶液(TTC)染色测定梗死面积和壁厚,ELISA检测血清炎症相关因子水平,TUNEL、免疫组织化学法检测心肌组织细胞凋亡率、血管密度。人脐静脉内皮细胞(HUVECs)分为阴性对照组、IL-21组、si-信号转导和转录活化因子3(STAT3)组、si-STAT+IL-21组,于缺氧血清饥饿(HSS)环境下培养24 h模拟缺血,通过MTT、TUNEL、血管形成实验评估细胞活力、凋亡、血管形成能力。qRT-PCR检测心肌组织IL-21、Ⅰ型胶原α1(COL1α1)、基质金属蛋白酶-9(MMP-9)、胱天蛋白酶3(Caspase-3)、B淋巴细胞瘤-2基因(Bcl-2)的表达水平,Western blot检测心肌组织IL-21、STAT3、p-STAT3、p38丝裂原活化蛋白激酶(P38)、p-P38、丝氨酸/苏氨酸蛋白激酶B(AKT)、p-AKT蛋白水平。结果:与假手术组比较,MI组梗死面积、LVESD、LVEDD、血清IL-1β、心肌组织COL1α1、MMP-9 mRNA、细胞凋亡率、Caspase-3 mRNA、p-STAT3、p-AKT、p-P38蛋白表达水平增加(均P<0.05),LVEF、FS、血清IL-21、IL-10、心肌组织IL-21 mRNA与蛋白、Bcl-2 mRNA降低(均P<0.05); 与MI组比较,MI+IL-21组梗死面积、LVESD、LVEDD、血清IL-1β、心肌组织COL1α1、MMP-9 mRNA、细胞凋亡率、Caspase-3 mRNA减小(均P<0.05),LVEF、FS、血清IL-21、IL-10、心肌组织IL-21 mRNA与蛋白、Bcl-2 mRNA、p-STAT3、p-AKT、p-P38蛋白、血管密度升高(均P<0.05)。与阴性对照组比较,IL-21组细胞存活率、成管长度增加(均P<0.05),细胞凋亡率下降(P<0.05),si-STAT3组细胞存活率、成管长度减小(均P<0.05),细胞凋亡率升高(P<0.05)。结论:IL-21可刺激血管生成,减少炎症反应及细胞凋亡,改善MI后心脏重塑,可能与激活STAT3通路相关。
Abstract:
Objective:To explore the effects of interleukin(IL)-21 on angiogenesis and cardiac remodeling in mice with myocardial infarction(MI)and its potential molecular mechanisms.Methods:Sixty rats were divided into sham operation group,MI group,and MI+IL-21 group,with 20 rats in each group.The MI model was established,and echocardiography was performed to measure the left ventricular end-systolic diameter(LVESD),left ventricular end-diastolic diameter(LVEDD),left ventricular ejection fraction(LVEF),and calculate the fractional shortening(FS)of the left ventricle.The myocardial infarction area and wall thickness were determined through 2,3,5-triphenyltetrazolium chloride(TTC)staining.The level of inflammation-related factors in serum was detected by ELISA.The TUNEL method was used to detect the apoptosis rate of myocardial tissue cells.Immunohistochemistry was used to assess the vascular density in the infarct border zone.Human umbilical vein endothelial cells(HUVECs)were divided into si-NC group,IL-21 group,si-signal transducer and activator of transcription 3(STAT3)group,and si-STAT+IL-21 group,and were cultured under hypoxic serum starvation(HSS)conditions for 24 hours to simulate ischemia.MTT,TUNEL,and angiogenesis assays were performed to evaluate cell viability,apoptosis,and angiogenesis ability.qRT-PCR was used to detect the gene expression levels of IL-21,collagen type I alpha 1(COL1α1),matrix metalloproteinase-9(MMP-9),Caspase-3,and B-cell lymphoma-2(Bcl-2)in myocardial tissues.Western blot was used to detect the protein levels of IL-21,STAT3,p-STAT3,p38 mitogen-activated protein kinase(P38),p-P38,serine/threonine protein kinase B(AKT),and p-AKT in myocardial tissues.Results:Compared with the sham surgery group,the MI group showed increases in infarct size,LVESD,LVEDD,serum IL-1β,COL1α1 in myocardial tissue,MMP-9 mRNA,apoptosis rate,Caspase-3 mRNA,expression levels of p-STAT3,p-AKT,and p-P38 proteins(all P<0.05),and decreases in LVEF,FS,serum IL-21,IL-10,IL-21 mRNA and protein in myocardial tissue,and Bcl-2 mRNA(P<0.05).Compared with the MI group,the MI+IL-21 group exhibited reductions in infarct size,LVESD,LVEDD,serum IL-1β,COL1α1 in myocardial tissue,MMP-9 mRNA,apoptosis rate,and Caspase-3 mRNA(all P<0.05).Additionally,there were increases in LVEF,FS,serum IL-21,IL-10,IL-21 mRNA and protein in myocardial tissue,Bcl-2 mRNA,p-STAT3,p-AKT,p-P38 proteins,and vascular density(P<0.05).Compared with the negative control group,the IL-21 group showed increased cell survival rate and tube formation length,along with a decrease in apoptosis rate(all P<0.05).Conversely,the si-STAT3 group exhibited decreased cell survival rate and tube formation length,accompanied by an increase in apoptosis rate(P<0.05).Conclusion::IL-21 can stimulates angiogenesis,reduces inflammatory response and apoptosis,and improves cardiac remodeling after myocardial infarction,which may be related to the activation of the STAT3 pathway.

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备注/Memo

备注/Memo:
基金项目:新疆维吾尔自治区科技支疆项目(2022E02058)
更新日期/Last Update: 2025-01-06