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