巨噬细胞移动抑制因子缺失加重苯肾上腺素诱导的小鼠心肌肥厚

doi:10.3969/j.issn.1007-2861.2016.03.011

上海大学学报(自然科学版) ›› 2016, Vol. 22 ›› Issue (3): 336-343.doi: 10.3969/j.issn.1007-2861.2016.03.011

巨噬细胞移动抑制因子缺失加重苯肾上腺素诱导的小鼠心肌肥厚

肖珍, 朱杰宁, 唐春梅, 林秋雄, 胡志琴, 张灼, 符永恒, 张梦珍, 单志新

广东省人民医院广东省医学科学院广东省心血管病研究所医学研究部, 广州510080

收稿日期:2016-04-19 出版日期:2016-06-30 发布日期:2016-06-30
通讯作者: 单志新(1972—), 男, 研究员, 博士生导师, 博士, 研究方向为心肌重构和心肌保护. E-mail: zhixinshan@aliyun.com
作者简介:单志新(1972—), 男, 研究员, 博士生导师, 博士, 研究方向为心肌重构和心肌保护. E-mail: zhixinshan@aliyun.com
基金资助:
国家自然科学基金资助项目(81270222, 81470439); 广东省自然科学基金资助项目(2014A030313635); 广东省医学研究基金资助项目(A2015187)

Macrophage migration inhibitory factor deficiency aggravates cardiac hypertrophy induced by phenylephrine in mice

XIAO Zhen, ZHU Jiening, TANG Chunmei, LIN Qiuxiong, HU Zhiqin, ZHANG Zhuo, FU Yongheng, ZHANG Mengzhen, SHAN Zhixin

Research Department of Medical Science, Guangdong Cardiovascular Institute, Guangdong Academy of Medical Sciences, Guangdong General Hospital, Guangzhou 510080, China

Received:2016-04-19 Online:2016-06-30 Published:2016-06-30

摘要/Abstract

摘要：

研究巨噬细胞移动抑制因子(macrophage migration inhibitory factor, MIF)缺失对皮下注射苯肾上腺素(phenylephrine, PE)诱导的小鼠心肌肥厚的影响. 利用MIF敲除(MIFknockout, MIF-KO)小鼠及其野生型对照小鼠, 分别建立皮下注射PE诱导的小鼠心肌肥厚模型. 小动物心脏B超检测到小鼠心脏结构功能的改变. 末端脱氧核苷酸转移酶介导的dUTP缺节末端标记(terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling, TUNEL)法检测到小鼠心肌细胞凋亡. 分别用实时定量逆转录多聚酶链反应(quantitative reverse-transcription-polymerase chain reaction, qRT-PCR)和Western Blot方法检测SOD1, SOD2和Trx2的表达. ①连续3 d 20 mg/(kg·d)皮下注射PE可诱导小鼠发生心肌肥厚, 注射PE诱导MIF-KO小鼠发生心肌肥厚的程度高于野生型对照小鼠; ②TUNEL结果显示, 注射PE诱导MIF-KO小鼠心肌发生凋亡的程度高于野生型对照小鼠; ③注射PE诱导MIF-KO小鼠心肌中SOD1和Trx2表达水平降低, 而且MIF-KO小鼠心肌中Trx2表达水平显著低于野生型对照小鼠. MIF缺失会降低SOD1和Trx2的表达水平, 进而加重苯肾上腺素诱导的小鼠心肌细胞凋亡和心肌肥厚.

关键词: 苯肾上腺素 , 心肌肥厚, 心肌细胞 , 巨噬细胞移动抑制因子

Abstract:

To investigate the effect of macrophage migration inhibitory factor (MIF) deficiency on the cardiac hypertrophy induced by hypodermic injection of phenylephrine (PE) in mice. A mouse model of cardiac hypertrophy induced by hypodermic injection of PE was established based on MIF-knockout (MIF-KO) mouse and the wide type control (WT) mouse. The left ventricular (LV) structure and function variables were assessed by transthoracic echocardiography. Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay was performed to detect cardiomyocyte apoptosis. Expressions of SOD1, SOD2 and Trx2 were determined by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western Blot assay, respectively. ①A mouse model of cardiac hypertrophy was achieved, induced by hypodermic injection of 20 mg/(kg·d) PE for 3 d. Compared with WT mice, PE injection induced more severe cardiac hypertrophy in MIF-KO mice. ②TUNEL assay revealed that the level of PE injection-induced cardiomyocte apoptosis in the myocardium of MIF-KO mouse was higher than that in WT mice. ③Expressions of SOD1 and Trx2 were significantly decreased in the myocardium of MIF-KO mice after PE injection, and reduction of Trx2 protein in myocardium of MIF-KO mice was more than that in WT mouse. MIF deficiency attenuates the expressions of SOD1 and Trx2, contributing to the aggravation of cardiomyocyte apoptosis and cardiac hypertrophy induced by hypodermic injection of PE in mice.

Key words: cardiac hypertrophy, cardiomyocyte , phenylephrine , macrophage migration inhibitory factor (MIF)

肖珍, 朱杰宁, 唐春梅, 林秋雄, 胡志琴, 张灼, 符永恒, 张梦珍, 单志新. 巨噬细胞移动抑制因子缺失加重苯肾上腺素诱导的小鼠心肌肥厚[J]. 上海大学学报(自然科学版), 2016, 22(3): 336-343.

XIAO Zhen, ZHU Jiening, TANG Chunmei, LIN Qiuxiong, HU Zhiqin, ZHANG Zhuo, FU Yongheng, ZHANG Mengzhen, SHAN Zhixin. Macrophage migration inhibitory factor deficiency aggravates cardiac hypertrophy induced by phenylephrine in mice[J]. Journal of Shanghai University（Natural Science Edition）, 2016, 22(3): 336-343.

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巨噬细胞移动抑制因子缺失加重苯肾上腺素诱导的小鼠心肌肥厚

Macrophage migration inhibitory factor deficiency aggravates cardiac hypertrophy induced by phenylephrine in mice

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