抗细胞趋化因子CCL21单克隆抗体处理对小鼠急性心肌梗死后左心室重构及心功能的影响

doi:10.12047/j.cjap.5579.2018.047

中国应用生理学杂志 ›› 2018, Vol. 34 ›› Issue (3): 197-200.doi: 10.12047/j.cjap.5579.2018.047

抗细胞趋化因子CCL21单克隆抗体处理对小鼠急性心肌梗死后左心室重构及心功能的影响

蒋易, 燕艳丽, 白建文

同济大学附属东方医院急诊内科, 上海 200120

收稿日期:2017-03-07 修回日期:2018-03-05 出版日期:2018-05-28 发布日期:2018-09-08
通讯作者: 白建文,Tel:021-38804518;E-mail:bjwhos@163.com E-mail:bjwhos@163.com
基金资助:
白建文,Tel:021-38804518;E-mail:bjwhos@163.com

Effect of treating with anti-CCL21 monoclonal antibody on left ventricular remodeling and cardiac function post-acute myocardial infarction in mice

JIANG Yi, YAN Yan-li, BAI Jian-wen

Department of Internal Medicine, Emergency Center, East Hospital, Tongji University School of Medicine, Shanghai 200120, China

Received:2017-03-07 Revised:2018-03-05 Online:2018-05-28 Published:2018-09-08
Contact: 白建文,Tel:021-38804518;E-mail:bjwhos@163.com E-mail:bjwhos@163.com
Supported by:
白建文,Tel:021-38804518;E-mail:bjwhos@163.com

摘要/Abstract

摘要： 目的：探讨抗CCL21单克隆抗体处理对小鼠急性心肌梗死后心室重构和心功能的影响。方法：C57BL/6小鼠随机分为假手术组、模型组和CCL21单抗干预组，并进一步分为1、3、7和21 d亚组。采用结扎冠状动脉左前降支的方法构建小鼠急性心肌梗死模型，在冠状动脉结扎后5 min和第3天，模型组小鼠静脉注射isotype-IgG 1.0 mg，CCL21单抗干预组小鼠静脉注射山羊抗小鼠CCL21单克隆抗体1.0 mg。建模后，Western blot法检测急性心肌梗死后第1、3、7天心肌组织CCR7表达，检测急性心肌梗死后第7天心肌组织MMP-2和MMP-9表达；建模后第1、3、7天，ELISA法检测各组小鼠血清TNF-α和IL-6水平，每组检测8只小鼠。在建模后第7天和21天，超声心动图法评估左心室功能变化。结果：与假手术组比较，模型组小鼠急性心肌梗死后血清CCL21、TNF-α和IL-6及心肌组织CCR7、MMP-2、MMP-9明显升高（P<0.05）；与模型组比较，CCL21单抗干预组小鼠血清TNF-α和IL-6及梗死区心肌组织MMP-9水平明显降低（P<0.05）。结论：抗CCL21单克隆抗体处理，通过抑制梗死后炎症反应及MMP-9表达水平发挥防止小鼠心脏重构和保护左心室功能的效应。

关键词: 心肌梗死, 炎症反应, MMP-9, 心脏重构, CCL21, 小鼠

Abstract: Objective: To explore the therapeutic effect of treating with anti-CCL21 monoclonal antibody on left ventricular remodeling and cardiac function post-acute myocardial infarction in mice.Methods: C57BL/6 mice were randomly divided into sham-operated group, model group and anti-CCL21 monoclonal antibody intervention group, and further randomly divided into 1 d, 3 d,7 d and 21 d subgroups. A mouse model of acute myocardial infarction (AMI) was generated by left anterior descending coronary artery ligation in C57BL/6 mice. Mice in model group were intravenously given isotype-IgG 1.0 mg, mice in anti-CCL21 monoclonal antibody intervention group were intravenously given goat anti-mouse CCL21 monoclonal antibody 1.0 mg at 5 minute and on the 3rd day post-coronary artery ligation. After surgery, C-C motif chemokine receptor 7 (CCR7) expression in myocardium was detected on the 1st, 3rd, 7th day, and the expressions of matrix metalloproteinase-2 (MMP-2) and MMP-9 in myocardium were detected on the 7th day 8 mice per group using Western blot. Serum levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in each group were measured on the 1st, 3rd, 7th day post-surgery using ELISA, 8 mice per group. Transthoracic echocardiography was underwent in mice on the 7th and 21th day after surgery using an echocardiography system to evaluate left ventricular function.Results: Compared with sham-operated group, serum levels of CCL21, TNF-α, IL-6, and myocardiac expression of CCR7、MMP-2、MMP-9 in model group were significantly increased (P<0.05). Compared with model group, serum levels of TNF-α and IL-6 and myocardiac expression level of MMP-9 were significantly decreased in anti-CCL21 monoclonal antibody intervention group(P<0.05).Conclusion: Our study indicates that treating with anti-CCL21 monoclonal antibody is involved in preventing cardiac remodeling and protecting left ventricular function post AMI via inhibiting inflammatory response and MMP-9 expression level.

Key words: myocardial infarction, inflammatory response, MMP-9, cardiac remodeling, CCL21, mice

蒋易, 燕艳丽, 白建文. 抗细胞趋化因子CCL21单克隆抗体处理对小鼠急性心肌梗死后左心室重构及心功能的影响[J]. 中国应用生理学杂志, 2018, 34(3): 197-200.

JIANG Yi, YAN Yan-li, BAI Jian-wen. Effect of treating with anti-CCL21 monoclonal antibody on left ventricular remodeling and cardiac function post-acute myocardial infarction in mice[J]. CJAP, 2018, 34(3): 197-200.

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抗细胞趋化因子CCL21单克隆抗体处理对小鼠急性心肌梗死后左心室重构及心功能的影响

Effect of treating with anti-CCL21 monoclonal antibody on left ventricular remodeling and cardiac function post-acute myocardial infarction in mice

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