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长期被动跑轮运动诱导建立大鼠生理性心肌肥厚模型
徐同毅1,2△,韩庆奇1△,张本1,蔡成良1,邹良建1*
0
(1. 第二军医大学长海医院胸心外科, 上海 200433;
2. 解放军401医院胸心外科, 青岛 266071
共同第一作者
*通信作者)
摘要:
目的 研究长期被动跑轮运动诱导的大鼠心肌肥厚,探索新的生理性心肌肥厚动物模型。 方法 雄性8周龄SPF级SD大鼠40只随机分为正常对照组、被动跑轮运动组、假手术组和主动脉弓缩窄组,各10只。对被动跑轮运动组和主动脉弓缩窄组大鼠分别行被动跑轮运动训练和主动脉弓缩窄术;正常对照组不作任何处理;假手术组不结扎胸主动脉,其他与主动脉弓缩窄组作相同处理。训练或术后5周,被动跑轮运动和主动脉弓缩窄两组模型分别与正常对照组和假手术组进行比较,从超声心动图、组织形态学、心衰分子标记物表达等方面来全面评估被动跑轮运动建立生理性心肌肥厚的效果。 结果 超声心动图结果显示,被动跑轮运动组和主动脉弓缩窄组的左室前壁厚度均较各自对照组明显增加(P<0.01) ;在每搏输出量和射血分数方面,被动跑轮运动组和主动脉弓缩窄组与各自的对照组比较,亦均有明显变化(P<0.01)。被动跑轮运动组的左心室舒张末期内径较正常对照组无明显改变,而主动脉弓缩窄组较假手术组减少38%(P<0.01),提示两种不同的心脏肥厚导致的心脏结构改变有明显差别。组织形态学方面,较正常对照组,被动跑轮运动组心脏质量指数增加25.0%,左室质量指数增加37.3%,肺脏质量指数增加23.8%;与假手术组比较,主动脉弓缩窄组的上述指标分别增加31.6%、38.8%和56.6%(P<0.05或P<0.01)。被动跑轮运动组心房利钠肽(ANP)和脑钠肽(BNP)的蛋白表达量明显降低,分别为正常对照组的0.67倍和0.48倍(P<0.05);而主动脉弓缩窄组ANP、BNP较假手术组分别升高1.98倍和2.03倍,差异有统计学意义(P<0.05)。 结论 长期被动跑轮运动能成功诱导大鼠生理性心肌肥厚,为建立生理性心肌肥厚的动物模型提供了新的方法。
关键词:  被动跑轮  主动脉弓缩窄  生理性心肌肥厚  病理性心肌肥厚
DOI:10.3724/SP.J.1008.2014.00697
投稿时间:2013-12-05修订日期:2014-03-20
基金项目:上海市卫生局科研基金(20124361).
Long-term passive wheel running-induced rat model of physiological cardiac hypertrophy
XU Tong-yi1,2△,HAN Qing-qi1△,ZHANG Ben1,CAI Cheng-liang1,ZOU Liang-jian1*
(1. Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai 200433, China;
2. Department of Cardiothoracic Surgery, No. 401 Hospital of PLA, Qingdao 266071, Shandong, China
Co-first authors.
* Corresponding author.)
Abstract:
Objective To explore a novel animal model of physiological cardiac hypertrophy induced by long-term passive wheel running. Methods Forty male Sprague-Dawley rats were randomly divided into four groups (n=10): normal control group, passive wheel running(PWR) group, sham operation group, and transverse aortic constriction(TAC) group.PWR group received passive wheel movement training, TAC group received aortic arch narrow operation, sham operation group did not receive ligature thoracic aorta, and other treatments were similar to that of TAC group; no treatment was given to the normal control group. Five weeks after training or operation, a comparison was made between different groups. The modeling results of PWR were assessed by echocardiography, morphology, and molecular hypertrophic-markers for heart failure. Results Echocardiography findings showed that thickness of the left ventricle wall in PWR group was significantly increased compared with the normal control group, and that in the TAC group was significantly increased compared with the sham operation group (P<0.01); the stroke volume and ejection fraction were also significantly different between PWR and normal control group and between the TAC group and sham operation group(P<0.01). The left ventricle internal diameter at end-diastole was not significantly different from that of normal control group, but that in the TAC group was decreased by 38% compared with the sham operation group (P<0.01), indicating that the cardiac structures were significantly different between PWR and TAC groups. Compared with the normal control group, the heart weight/body weight ratio, left ventricular weight/body weight ratio and lung weight/body weight ratio were increased by 25.0%, 37.3% and 23.8% in PWR rats, respectively; compared with the sham group, the above indicators were increased by 31.6%, 38.8% and 56.6% in TAC rats, respectively(P<0.05 or P<0.01). Compared with the normal control group, the expression levels of atria natriuretic peptide (ANP)and brain natriuretic peptide (BNP)were 0.67-fold and 0.48-fold of those in PWR group(P<0.05), and those in the TAC group were 1.98-fold and 2.03-fold those of the sham operation group (P<0.05). Conclusion Long-term PWR training can induce physiological cardiac hypertrophy in rats, which may provide a novel way for establishing physiological cardiac hypertrophy animal models.
Key words:  passive wheel running  transverse aortic constriction  physiological cardiac hypertrophy  pathological cardiac hypertrophy