myocardial autophagy after severe burn in rats心肌严重烧伤大鼠后自噬.pdfVIP

Myocardial Autophagy after Severe Burn in Rats . . Rong Xiao , Miao Teng , Qiong Zhang, Xiao-hua Shi, Yue-sheng Huang* Institute of Burn Research, State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, The Third Military Medical University, Chongqing, China Abstract Background: Autophagy plays a major role in myocardial ischemia and hypoxia injury. The present study investigated the effects of autophagy on cardiac dysfunction in rats after severe burn. Methods: Protein expression of the autophagy markers LC3 and Beclin 1 were determined at 0, 1, 3, 6, and 12 h post-burn in Sprague Dawley rats subjected to 30% total body surface area 3rd degree burns. Autophagic, apoptotic, and oncotic cell death were evaluated in the myocardium at each time point by immunofluorescence. Changes of cardiac function were measured in a Langendorff model of isolated heart at 6 h post-burn, and the autophagic response was measured following activation by Rapamycin and inhibition by 3-methyladenine (3-MA). The angiotensin converting enzyme inhibitor enalaprilat, the angiotensin receptor I blocker losartan, and the reactive oxygen species inhibitor diphenylene iodonium (DPI) were also applied to the ex vivo heart model to examine the roles of these factors in post-burn cardiac function. Results: Autophagic cell death was first observed in the myocardium at 3 h post-burn, occurring in 0.008 6 0.001% of total cardiomyocytes, and continued to increase to a level of 0.022 6 0.005% by 12 h post-burn. No autophagic cell death was observed in control hearts. Compared with apoptosis, autophagic cell death occurred earlier and in larger quantities. Rapamycin enhanced autophagy and decreased cardiac function in isolated hearts 6 h post-burn, while 3-MA exerted the opposite