丹酚酸A对心力衰竭大鼠心肌凋亡及心室重构的保护-南京医科大学学报.doc

丹酚酸A对压力超负荷大鼠心功能减退和心室重构的改善作用 丁 超[基金项目] 南京医科大学科技发展基金重点资助（2011NJMU264） * 通讯作者（Corresponding author），E-mail：lirongcheng0912@163.com ，谢利平2，李荣成1* （1安徽省六安市市立医院心内科，安徽 六安 237000；2南京医科大学病理生理学系，江苏 南京 210029） [摘 要]目的：探讨丹酚酸A（Sal A）对压力超负荷大鼠心功能减退和心室重构的改善作用。方法：采用主动脉缩窄法（TAC）制备压力超负荷大鼠模型，并连续给予5 mg/(kg?d)的Sal A灌胃处理，同时部分压力超负荷大鼠仅注射等体积的生理盐水（saline），假手术（Sham）仅行开胸处理而不行TAC，依据实验设计将大鼠分为4组：Sham-saline组、TAC-saline组、Sham-Sal A组和TAC-Sal A组。分析12周后4组的血流动力学、心功能、心脏解剖学指标；采用苏木素-伊红（HE）、Massons三重及特异性荧光探针DHE染色分析心肌细胞的形态学、纤维化及活性氧自由基水平；免疫印迹法检测心肌细胞凋亡相关基因的蛋白水平。结果：与Sham-saline组比较，TAC处理可导致心率、左室收缩期平均压力、左室内压最大上升速率、Bcl-2（抑制凋亡基因）水平降低（P0.05），左室舒张末期压力、心肌直径、胶原容积分数、心脏体重比、心肌荧光强度、Bax和Cleaved caspase-3（促凋亡基因）水平升高；给予Sal A处理的压力超负荷大鼠，以上指标均获改善，且差异有统计学意义；但左室收缩期平均压力、心脏体重比、心肌直径、胶原容积分数、凋亡相关基因的水平仍与Sham-saline组有差异（P0.05）；Sal A处理对Sham大鼠的各项指标无影响。结论：Sal A可改善压力超负荷大鼠的心功能减退及包括心肌肥大、纤维化及凋亡在内的心室重构，具有较好的保护作用。 [关键词] 丹酚酸A；心功能减退；心肌肥大；心肌凋亡；心室重构 Improving effect of salvianolic acid A on pressure overload-induced cardiac dysfunction and ventricular remodeling in rats Ding Chao1，Xie Liping2，Li Rongcheng1* （1Department of Cardiology, Luan Municipal Hospital, Luan 237000, China;2Department of Pathophysiology, Nanjing Medical University, Nanjing 210029, China） [Abstract] Objective: To explore the improving effect of Salvianolic acid A (Sal A) on pressure overload-induced cardiac dysfunction and ventricular remodeling in rats. Methods: The pressure overload rat model was established by transverse aortic constriction (TAC). The Sal A was applied at the concentration of 5 mg/(kg?d) by gavage for continuous 12 weeks, and some rats with pressure overload were treated with the same volume of saline. According to the experimental design, the rats were assigned into 4 groups: Sham-saline, TAC-saline, Sham-Sal A and TAC-Sal A. Twelve weeks later, the hemodynamic conditions, heart function and heart anatomy indicators were investigated among 4 groups. Hematoxylin-eosin (HE), Massons triple staining and specific fluorescent probe DHE were used to analyze the m