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《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:

2016年第6期

页码:

642-646

栏目:

基础研究

出版日期:

2016-07-05

文章信息/Info

Title:

Advanced glycosylation end products aggravate mechanism of post-traumatic secondary heart damage in aging mice

作者:

李 莹¹; 王志法²; 袁 铭¹; 马 恒²; 3

(第四军医大学：1.西京医院心脏内科，2.生理学教研室，3.病理生理学教研室，陕西 西安 710032)

Author(s):

LI Ying¹;  WANG Zhi-fa²;  YUAN Ming¹;  MA Heng²; 3

(1.Department of Cardiology, Xijing Hospital, 2.Department of Physiology, 3.Department of Pathophysiology, Fourth Military Medical University, Xi’an 710032, Shaanxi, China)

关键词:

晚期糖基化终产物; 机械性创伤; 心肌损伤; 衰老; 羧甲基赖氨酸

Keywords:

advanced glycation endproducts;  mechanical trauma;  myocardial injury;  aging;  carboxymethyllsine

分类号:

R541.9

DOI:

-

文献标识码:

A

摘要:

目的 探讨衰老个体创伤后心肌损伤加重的机制，尤其是晚期糖基化终产物（AGEs）在其中发挥的作用。方法 C57雄性小鼠使用Noble-Collip创伤仪制备小鼠创伤模型。将成年C57小鼠（2月龄18只）和老年C57小鼠（20月龄18只）随机分为：非创伤组、创伤组、创伤干预组。采用彩色多普勒超声诊断仪检测左室射血分数(EF)和左室短轴缩短率(FS)。取心肌组织予Western blot检测磷酸化的AMP蛋白激酶（pAMPK）、AMP蛋白激酶（AMPK）、p16和p53 蛋白表达水平，使用ELISA 试剂盒检测血清可溶性晚期糖基化终产物受体（sRAGE）和羧甲基赖氨酸（CML）的水平。结果 与成年创伤小鼠对比，老年小鼠创伤后心肌损伤明显加重，表现为左室EF和左室FS显著减低（均P<0.01）。血MG-AGEs显著升高（P<0.05）以及AMPK活性下降（P<0.05）。预先采用sRAGE对AGEs进行干预，可显著改善老年小鼠创伤后心功能，表现为心肌AMPK活性显著提高（P<0.01），心脏功能EF和FS值显著提高（P<0.01）。结论 衰老个体创伤后心肌损伤加重的机制与MG-AGEs系统有关，该系统可能是提高老年个体临床救治的有效靶点之一。

Abstract:

AIM To observe the aggravating mechanism of myocardial injury in aging individuals after mechanical trauma, especially the role of advanced glycosylation end products. METHODSA mechanical trauma mice model was established in C57 male mice by Noble-Collip drum. C57 adult mice (2 months) and aged C57 mice (20 months) were randomized into non-trauma group, trauma group and intervention group. Left ventricular ejection fraction and left ventricular short axis shortening rates were detected using color Doppler ultrasonographic diagnosis apparatus. Expressions of AMP protein kinase (p-AMPK), AMP protein kinase (AMPK), p53 and p16 were analyzed by Western blot. Soluble advanced glycosylation end products (sRAGE) and carboxymethyllsine (CML) were detected by ELISA kits. RESULTSCompared with control group (adult mice), myocardial injury in elderly mice significantly increased after mechanical trauma. Left ventricular ejection fraction and left ventricular short axis shortening rate were significantly lower (P<0.01). MG-AGEs significantly increased after mechanical trauma (P<0.05) and AMPK activity declined (P<0.05). In-advance intervention with AGEs significantly improved myocardial function in elderly mice after trauma. CONCLUSIONThe aggravating mechanism of myocardial injury in aging individuals after mechanical trauma is associated with MG-AGEs system. MG-AGEs system may be an effective target for clinical treatment in aging patients.

参考文献/References

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备注/Memo

备注/Memo:

收稿日期：2016-01-12.
基金项目：国家自然科学基金资助（81322004，81200189）
通讯作者：袁铭，副教授，主要从事冠心病及高血压的临床诊治及机制研究Email:yuanming@fmmu.edu.cn
共同通讯作者：马恒，副教授，主要从事心肌内源性保护机制研究Email:hengma@fmmu.edu.cn
作者简介：李莹，硕士生Email：453431143@qq.com

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更新日期/Last Update: 2016-07-10