【摘要】 目的探讨心阳片通过调节晚期糖基化终产物受体（RAGE）介导的自噬改善心力衰竭小鼠心功能的作用。方法将60只C57BL/6J小鼠随机分为6组,分别为假手术组、模型组、3-甲基腺嘌呤组(自噬抑制剂,15 mg·kg^-1)以及心阳片低、中、高剂量组(455、910、1 820 mg·kg^-1),每组10只;另将10只经基因型鉴定确认为RAGE^-/-的小鼠作为RAGE敲除组。采用主动脉弓缩窄术（TAC）建立压力负荷性心力衰竭小鼠模型。模型复制成功后,按上述剂量对心阳片各剂量组小鼠进行灌胃给药,3-甲基腺嘌呤组进行腹腔注射给药,其余组别灌胃等容积生理盐水,每天给药1次,连续4周。采用心脏彩超检测各组小鼠心功能,采集小鼠左室射血分数（LVEF）及左室短轴缩短率（LVFS）;使用Masson染色观察小鼠心肌组织纤维化程度;采用蛋白免疫印迹法（Western Blot）检测小鼠心脏左室心肌组织中的RAGE蛋白及自噬相关蛋白Beclin-1、LC3BⅡ/Ⅰ的表达情况。结果与假手术组比较,模型组小鼠的LVEF及LVFS明显降低（P<0.05）,心肌纤维化面积明显增加（P<0.05）,RAGE蛋白及自噬相关蛋白Beclin-1、LC3BⅡ/Ⅰ的表达明显上调（P<0.05）;与模型组比较,RAGE敲除组、3-甲基腺嘌呤组及心阳片低、中、高剂量组小鼠的LVEF和LVFS明显升高（P<0.05）,心肌纤维化面积明显减少（P<0.05）,RAGE、Beclin-1、LC3BⅡ/Ⅰ蛋白表达明显下调（P<0.05）。结论心阳片可能通过调节RAGE介导的自噬,从而改善心力衰竭小鼠的心功能。更多还原

【Abstract】 Objective To investigate the possible mechanism of Xinyang tablet on improving the cardiac function in heart failure mice by regulating receptor for activated glycation end products（RAGE）-mediated autophagy.Methods Sixty C57 BL/6 J mice were randomly divided into Sham operation group, model group, 3-methyladenine group(15 mg·kg^-1)and low,medium,high dosages of Xinyang tablets groups(455,910,1 820 mg·kg^-1). In addition,ten mice confirmed to be RAGE^-/- by genotyping were taken as a RAGE knock-out group. Heart failure mice model were induced by Transverse Aortic Constriction（TAC）. According to the dosages above,mice were given intragastric administration or intraperitoneal injection once a day for 4 weeks,while the Sham operation group,RAGE knockout group and the model group were gavaged the same volume of normal saline. We evaluated the cardiac function of mice by cardiac Doppler ultrasound, and left ventricular ejection fraction（LVEF） and left ventricular fraction shortening（LVFS）were measured. The degree of fibrosis in heart of mice was observed by Masson staining. The expression of RAGE and autophagy-related proteins Beclin-1 and LC3 BⅡ/Ⅰ were detected by Western Blot.Results Compared with the Sham operation group,the LVEF and the LVFS of the model group were significantly decreased（P < 0.05）. The degree of myocardial fibrosis was significantly aggravated（P < 0.05）. Moreover,the expression of Beclin-1 and LC3 BⅡ/Ⅰ were increased（P < 0.05）. As compared with the model group,the cardiac function showedsignificant improvement in all dosage groups of Xinyang tablets,RAGE knock-out group and 3 MA group（P < 0.05）.The degree of myocardial fibrosis was significantly reduced（P < 0.05）. The levels of Beclin-1 and LC3 B proteinexpression were decreased in these groups（P < 0.05）.Conclusion Xinyangtablets can effectively improve cardiacfunction in mice with heart failure by regulating RAGE-mediated autophagy.更多还原