游泳力竭对冠脉结扎致大鼠慢性心衰模型的优化

中国临床药理学与治疗学 ›› 2017, Vol. 22 ›› Issue (12): 1340-1345.

游泳力竭对冠脉结扎致大鼠慢性心衰模型的优化

刘长江¹，武洋²，邵培培²，李少华²，程路峰²

¹新疆医科大学第六附属医院药学部，乌鲁木齐 830002，新疆; ²新疆医科大学基础医学院药理学教研室，乌鲁木齐 830011，新疆

收稿日期:2017-06-12 修回日期:2017-06-24 出版日期:2017-12-26 发布日期:2018-01-02
通讯作者: 程路峰，男，博士，教授，硕导，研究方向：心血管药理。 Tel：13999151882 E-mail：lewis_clf@163.com
作者简介:刘长江，男，硕士，研究方向：心血管药理。 Tel：13669955695 E-mail：liuchangjiang_xjmu@163.com
基金资助:
国家自然科学基金资助项目（81360491）；自治区高校科研计划(重点项目)(XJEDU2013I22)

Optimization of chronic heart failure model induced by coronary artery ligation in rats with swimming exhaustion

LIU Changjiang ¹, WU Yang ², SHAO Peipei ², LI Shaohua², CHENG Lufeng ²

¹Department of Pharmacy, The Sixth Clinical Hospital, Xinjiang Medical University, Urumqi 830002, Xinjiang, China; ²Department of Pharmacology, Preclinical Medicine College, Xinjiang Medical University, Urumqi 830011, Xinjiang, China

Received:2017-06-12 Revised:2017-06-24 Online:2017-12-26 Published:2018-01-02

摘要/Abstract

摘要：

目的: 通过结合力竭运动，优化冠脉结扎造大鼠缺血性慢性心力衰竭（心衰）模型的方法，综合评价模型实效性及稳定性。方法: 成年SD大鼠40只，施冠状动脉结扎术致心肌缺血模型，4周后B超检测左心室射血分数（LVEF），成模11只为冠脉结扎组（以LVEF<40%为模型建立标准），>40%的22只大鼠进行1 h/d×15 d的游泳运动，以加大心脏负荷促进心衰的进展，又成模8只大鼠为结扎后力竭组。实验结束后检测心功能指标，脑钠肽（BNP）及心肌组织形态学变化，与10只空白大鼠比较各指标变化。结果: 结扎后力竭组左心室射血分数（LVEF）为（38.70±10.10）%，冠脉结扎组LVEF为（39.20±11.10）%，较Control组（84.60±3.64）%明显降低（P＜0.01）；结扎后力竭组左室舒张末压（LVEDP）为（11.5±1.3） mm Hg，冠脉结扎组LVEDP为（10.68±4.45） mm Hg，较Control组（4.4±0.2） mm Hg显著升高（P＜0.01）；结扎后力竭组血浆BNP水平为(561.0±21.0) μg/L，冠脉结扎组BNP水平为（548.6±25.8） μg/L，较Control组（366.2±21.8） μg/L显著升高（P＜0.01）。Masson染色中，Control组切片纹路清晰且红染的心肌细胞较多，而冠脉结扎组与结扎后力竭组存在大量蓝染的胶原纤维，心肌纤维明显减少成条索状。4周时成模率约为35%，经力竭运动后实验组总成模率升高至约62%，虽冠脉结扎组与结扎后力竭组各指标无统计学差异，但提高成模率效果显著（P＜0.01）。结论: 游泳力竭运动可促进冠状动脉高位结扎致缺血性慢性心衰模型的成功率，成本经济，适合推广。

关键词: 冠状动脉结扎, 游泳力竭, 心力衰竭, 大鼠

Abstract:

AIM: To establish the rat model of ischemic chronic heart failure by coronary artery ligation combining with exhaustive swimming. METHODS: 40 adult rats were treated with coronary artery ligation, after 4 weeks cardiac function measurement were conducted by ultrasonography. Rats with LVEF below 40% are considered as successful model duplication. 11 rats were collected for the coronary artery ligation group, while the rest (whose LVEF were bigger than 40%) were pushed to swim for 1 h per day by 15 days to promote the model formation which 8 rats were collected for exhaustion with ligation group. Left ventricular function indexes, brain natriuretic peptide (BNP) and cardiac histomorphologic changing were checked, and compared with the Control group (10 rats). RESULTS: LVEF of exhaustion with ligation group was (38.70±10.10)%, coronary artery ligation group (39.20±11.10)%, which was obviously decreasing (P＜0.01) compared with that of the control group (84.60±3.64)%. LVEDP of exhaustion with ligation group was (11.5±1.3) mm Hg, coronary artery ligation group［(10.68±4.45) mm Hg］, which was obviously increasing (P＜0.01) compared with that of the Control group［(4.4±0.2) mm Hg］. The BNP level of exhaustion with ligation group was (561.0±21.0) μg/L, coronary artery ligation group (548.6±25.8) μg/L, which was obviously increasing (P＜0.01) compared with that of control group［(366.2±21.8) μg/L］. There are lots of red myocardial cells with stripe clear in the control group based on Masson's trichrome staining, but there are so many blue collagenous fibers instead of myocardial cells in exhaustion with ligation group and coronary artery ligation group. The standard-reaching rate of model was about 35% at 4 weeks after operation, while final standard-reaching rate rose to about 62% after exhausting swimming. Although the difference between the indexes of the coronary artery ligation group and the post ligation group was not significant, the rate of improvement was significant (P＜0.01). CONCLUSION: Ligation of coronary artery combined with swimming exhaustion can establish ischemic chronic heart failure model, which is more economic and can obtain high success rate, thus is suitable to generalization.

Key words: coronary artery ligation, exhaustive swimming, heart failure, rat

中图分类号:

R965.2

刘长江，武洋，邵培培，李少华，程路峰. 游泳力竭对冠脉结扎致大鼠慢性心衰模型的优化[J]. 中国临床药理学与治疗学, 2017, 22(12): 1340-1345.

LIU Changjiang, WU Yang, SHAO Peipei, LI Shaohua, CHENG Lufeng. Optimization of chronic heart failure model induced by coronary artery ligation in rats with swimming exhaustion[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2017, 22(12): 1340-1345.

参考文献

［1］袁羚钟, 唐泽念. 慢性心力衰竭的诊断治疗［J］. 中国医药指南, 2013, 23: 537-538.
［2］Yogaratnam JZ, Laden G, Guvendik L, et al. Pharmacological preconditioning with hyperbaric oxygen: can this therapy attenuate myocardial ischemic reperfusion injury and induce myocardial protection via nitric oxide［J］? Surg Res, 2008, 149(1): 155- 164.
［3］吴晓晴. 动物实验基本操作技术手册［M］. 北京人民军医出版社, 2008: 76-77.
［4］Samsamshariat SA, Ahmad Samsamshariat ZA, Movahed MP. A novel method for safe and accurate left anterior descending coronary artery ligation for research in rats［J］. Cardiovasc Revasc Med, 2005, 6(3): 121-123.
［5］Beck W, Gobatto CA. Effects of maximum intensity aerobic swimming exercise until exhaustion at different times of day on the hematological parameters in rats［J］.Acta Physiol Hung, 2013,100(4): 427.
［6］周白瑜. 2014 版《心衰治疗指南》肯定NP-proBNP 临床应用价值［J］. 中华心血管杂志, 2014, 19(4): 320.
［7］Shao Y, Redfors B, Omerovic E. Modified technique for coronary artery ligation in mice［J］. J Vis Exp, 2013, 29(73): 1-4.
［8］张晓京, 来丽娜, 张晓一, 等. 山茱萸多糖对大鼠心肌缺血再灌注损伤的保护作用及机制探讨［J］. 中国临床药理学与治疗学, 2016,21(7):759-764.
［9］许朝阳. SD大鼠3种慢性心力衰竭模型的建立及心功能比较［J］. 心电与循环, 2014, 33(4): 307-310.
［10］Giorgianni F, Usman Khan M, Weber KT, et al. Phosphoproteome mapping of cardiomyocyte mitochondria in aratmodelofheartfailure［J］. Mol Cell Biochem,2014,389:159-167.
［11］Schwarz ER, Speakman MT, Kloner RA. A new model of ventricular plication:a suturing technique to decrease left ventricular dimensions improve contractility and attenuate ventricular remodeling after myocardial infarction in the rat heart［J］. J Cardiovasc Pharmt, 2000, 5(5):41-49.
［12］吴娟, 张根葆, 张娅, 等. 蝮蛇毒血小板抑制因子对急性心肌梗死大鼠血液流变影响及机制的研究［J］. 中国临床药理学与治疗学, 2016,21(3):259-263, 275.
［13］Braunwald E, Bristow MR. Congestive heart failure［J］. Circulation, 2000, 102:IVl4-IV23.
［14］Cohn JN, Ferrari R, Sharpe N. Cardiac remodeling-concepts and clinical implications: a consensus paper from an international forum on cardiac remodeling. Behalf of an International Forum on Cardiac Remodeling［J］. J Am Coll Cardiol, 2000, 3(3):569-582.

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