天津医药

天津医药 ›› 2019, Vol. 47 ›› Issue (7): 713-717.doi: 10.11958/20190662

• 实验研究 • 上一篇    下一篇

心肌自噬在异丙肾上腺素诱导心肌肥厚中的作用

宋代富，郭国锋,龙海权，陈盛强，黄炯华，陈晞明   

  1. 1广州医科大学附属第三医院心血管内科（邮编 510150）；2广州医科大学附属第二医院神经科学研究所
  • 收稿日期:2019-03-12 修回日期:2019-05-26 出版日期:2019-07-15 发布日期:2019-08-01
  • 通讯作者: 陈盛强 E-mail:chenshengqq@163.com

The role of myocardial autophagy in isoproterenol-induced cardiac hypertrophy

SONG Dai-fu，GUO Guo-feng，LONG Hai-quan，CHEN Sheng-qiang，HUANG Jiong-hua，CHEN Xi-ming   

  1. 1 Department of Cardiology, the Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, China; 2 Institute of Neuroscience, the Second Affiliated Hospital of Guangzhou Medical University
  • Received:2019-03-12 Revised:2019-05-26 Published:2019-07-15 Online:2019-08-01

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摘要： 目的 探讨心肌自噬在异丙肾上腺素（ISO）诱导大鼠心肌肥厚中的作用。方法 将 29只大鼠随机分为 3组：皮下联合腹腔注射生理盐水（Con）组 9只、腹腔注射生理盐水联合皮下注射异丙肾上腺（ISO）组 10只、腹腔注射雷帕霉素（RAP）联合皮下注射 ISO（ISO+RAP）组 10 只。连续干预 14 d 后，将 Con 组和 ISO 组存活大鼠（Con，n=9；ISO，n=8）行心脏超声检查左室壁厚度及左室射血分数（LVEF），再将各组大鼠腹腔注射过量的 10%水合氯醛处死，摘除心脏，计算心脏体质量指数（HWI）。心肌组织病理切片行 HE染色和 Masson染色，Western blot检测 p62表达和LC3Ⅱ/Ⅰ比值，透射电镜观察心肌组织自噬泡数量。结果 与 Con组比较，ISO组左室壁厚度和 LVEF明显增加（P＜0.01）。与 Con组比较，ISO组和 ISO+RAP组的 HWI增大（P＜0.01），且 ISO+RAP组的 HWI小于 ISO组（P＜0.01）。与Con组比较，ISO组心肌病理切片显示心肌组织病理性肥厚改变明显；而与 ISO组比较，ISO+RAP组心肌组织病理性肥厚明显改善。与 Con 组比较，ISO 组心肌组织 LC3Ⅱ/Ⅰ比值下调，而 p62 表达上调，自噬泡数量明显减少（P＜0.05）；与 ISO组比较，ISO+RAP组心肌组织 LC3Ⅱ/Ⅰ比值上调，而 p62表达下调，自噬泡数量明显增多（P＜0.01）。结论 上调心肌自噬活性可以逆转 ISO诱导的病理性心肌肥厚。

关键词: 细胞, 心脏, 心肌病, 肥厚性, 异丙肾上腺素, 疾病模型, 动物, 自噬

Abstract: Objective To explore the effects of myocardial autophagy on isoproterenol (ISO) - induced cardiac pathological hypertrophy in rats. Methods Twenty-nine SD rats were randomly divided into three groups: subcutaneous injection of normal saline combined with intraperitoneal injection of normal saline (Con, n=9) group, subcutaneous injection of normal saline combined with intraperitoneal injection of isoproterenol (ISO, n=10) group and subcutaneous injection of rapamycin (RAP) combined with intraperitoneal injection of ISO (ISO + RAP, n=10) group. After 14-days of continuous treatment, cardiac echocardiogram for left ventricular wall thicknesses and ejection fraction (LVEF) were carried out in Con group (n=9) and ISO group (n=8). Rats were executed by intraperitoneal injection of overdoes 10% chloral hydrate. Heart to body index (HWI) was calculated by heart weight/body weight. Cardiac pathologic alternation was observed by histological sections stained with hematoxylin and eosin (HE) and Masson. The expression of p62 and the ratio of LC3 Ⅱ/Ⅰ were measured by Western blot assay. The number of autophagic vacuoles was detected by transmission electron microscopy.Results Compared with Con group, the left ventricular wall thickness and LVEF were significantly increased in ISO group (P＜0.01). Compared with Con group, the HWI was increased in ISO group and ISO+RAP group (P＜0.01). But the HWI was decreased in ISO+RAP group comparison with that of ISO group (P＜0.01). Compared with Con group, the alternation of cardiac pathological hypertrophy was marked in ISO group.Moreover, compared with ISO group, cardiac pathological hypertrophy was improved in ISO+RAP group. Compared with Con group, the ratio of LC3Ⅱ/Ⅰwas down-regulated, the protein expression of p62 was up-regulated and the number of autophagic vesicles was significantly reduced in ISO group (P＜0.01). However, compared with ISO group, the ratio of LC3Ⅱ/Ⅰwas up-regulated, the protein expression of p62 was down-regulated and the number of autophagic vesicles was significantly increased in ISO + RAP group (P＜0.01). Conclusion The up-regulation of myocardial autophagy can reverse pathological hypertrophy induced by ISO.

Key words: myocytes, cardiac, cardiomyopathy, hypertrophic, isoproterenol, disease models, animal, autophagy