中文摘要：

可溶性晚期糖基化终末产物受体（soluble receptor for advanced glycation end-products,s RAGE）作为内源性保护物质,能够拮抗心肌缺血/再灌注（ischemia/reperfusion,I/R）损伤发生,重要机制是减轻心肌细胞凋亡。而近年来随着细胞死亡研究的深入,细胞自噬被认为是一种新的细胞程序性死亡。s RAGE是否可以抑制缺血/再灌引起的心肌细胞自噬尚未见报道。本文研究证明,s RAGE可抑制缺血/再灌注引起的心肌细胞自噬。以心肌细胞缺氧/复氧模拟心肌细胞缺血/再灌注模型,蛋白质印迹检测自噬门户蛋白beclin-1的表达,激光共聚焦显微镜检测自噬小体及自噬溶酶体的形成。心肌再灌注期间,心肌细胞自噬小体增加,而自噬溶酶体下降。细胞内自噬小体堆积,说明心肌细胞缺血/再灌注使自噬小体与溶酶体结合受损,清除发生障碍。与缺血/再灌注（I/R）组比较,缺血/再灌＋s RAGE（I/R＋s RAGE）组的自噬流减弱。此外,自噬门户蛋白beclin-1也表达下降。以上结果从细胞形态学和蛋白水平两方面说明,s RAGE抑制了I/R引起的心肌细胞自噬。换言之,s RAGE可以直接作用于心肌细胞拮抗缺血/再灌注损伤,其保护性作用可能与抑制心肌细胞自噬有关。

英文摘要：

Soluble receptor for advanced glycation end-products（ s RAGE）,as an endogenous protection factors,enhances cardioprotection by inhibiting myocardial apoptosis from ischemia/reperfusion（ I/R）.Growing evidence suggests thatautophagic cell death is a new type of cell death. However,the role of s RAGE on I/R-induced myocardial autophagy remains unclear. Thus,this study demonstrated that s RAGE protected I/R injury against I/R-induced myocardial autophagy. Myocardial I/R model was simulated by myocardial hypoxia/reoxygenation. The expression of beclin-1 was detected by Western blot assay. The formation of autophagosomes and autolysosomes were observed by confocal laser scanning microscopy. The autophagosomes were increased in each cell,but the autolysosomes were reduced ineach cell during myocardial reperfusion phase,which indicated that I/R injury impaired autophagosome clearance. Compared with I/R group, the beclin-1 expression and the autophagic flux were both decreased in I/R ＋ s RAGE group. Above results proved that I/R-induced myocardial autophagy might be inhibited by s RAGE. Alternatively,s RAGE acted directly on myocardial cells and antagonized the I/R injury,which was related to inhibition of excessive autophagy.