中文摘要：

目的探讨在缺血后适应（IPost）减轻肥厚心肌缺血再灌注（IR）损伤中S1P信号通路的作用。方法选取12周龄C57/BL小鼠,利用Langendorff灌流装置建立小鼠肥厚心肌IR模型,30 min全心缺血随后再灌注90 min。64只小鼠随机分为缺血再灌注组（IR组）、缺血后适应组（IPost组）、IPost＋W-146组和IPost＋PD98059组,每组14只,进行心脏血流动力学和心肌梗死范围检测,Western印迹方法检测S1P1、ERK1/2总蛋白及磷酸化蛋白表达水平。脱氧核苷酸转移酶介导的生物素原位缺口末端标记（TUNEL）法检测心肌细胞的凋亡。结果与IR组比较,IPost组小鼠心脏血流动力学指标左心室收缩压[（66±6）mm Hg vs（85±5）mm Hg]、左室压力上升最大速度[（2 820±220）mm Hg vs（3 778±230）mm Hg]显著降低（P〈0.05）,心肌梗死范围显著减小[（23.6±2.8）%vs（40.2±4.6）%]。IPost＋抑制剂组显示在再灌注的最初15 min使用W-146、PD98059能消除IPost对肥厚心肌的上述保护作用并显著增加心肌梗死面积,与IR组水平相同。与IR组比较,IPost组在再灌注结束后心肌组织中的S1P1、ERK1/2蛋白磷酸化水平表达显著增加;IPost＋W-146组与IPost＋PD98059组分别与IR组比较,上述指标差异均无统计学意义（P〉0.05）;TUNEL法检测结果显示,IPost组Bcl-2的表达较其他各组明显升高,Bax的表达较其他各组明显降低,经比较各组之间Bcl-2和Bax的表达差异无统计学意义（P〉0.05）。结论 IPost能有效地减轻离体小鼠肥厚心肌缺血再灌注损伤,IPost的心肌细胞保护作用可能是通过S1P结合S1P1后激活ERK1/2信号通路实现的。

英文摘要：

Objective To investigate the effects of ischemic postconditioning（IPost） in protecting hypertrophic myocardium subjected to ischemic re-perfusion（IR） and to study the role of Sphingosine-1-phosphate in mediating such protection. Methods Transverse aortic constriction（TAC） operation was performed on 12-week-old C57/BL mice to establish left ventricular hypertrophy models. Sixty-four isolated TAC mouse hearts were mounted onto the Langendorff perfusion system and equally divided into four groups： IR group [undergoing stable perfusion for 30 min, ischemic for 30 min, and re-perfusion for 90 min（an IR cycle） to cause hypertrophic myocardium IR injury], IPost group [undergoing ischemic for 10 s and re-perfusion 10 s, totally 3 cycles（60 s） before re-perfusion for 90 min],IPost＋W-146 group and IPost＋PD98059 group. Hemodynamic examination was conducted 90 min after re-perfusion to measure the left ventricular systolic pressure（LVSP）, left ventricular end diastolic pressure（LVEDP）, maximal uprising velocity of left ventricle pressure（dp/dtmax）, and minimal uprising velocity of left ventricle pressure（dp/dtmin）. After the IR procedure the myocardium of the left ventricle was isolated to detect the infarction size（IS）. Western blotting was used to detect the protein expression of S1P1, ERK1/2 and phosphorylated ERK1/2. TUNEL was used to detect the apoptosis rate. Results Compared with IR group, the LVSP levels of the IPost group were significantly higher [（66±6） mm Hg vs（85±5） mm Hg], the dp/dtmax were significantly decreased [（2 820±220） mm Hg vs（3 778±230） mm Hg], and the infarction size was significantly reduced [（23.6±2.8）% vs（40.2±4.6）%], all with P〈0.05.However, the results of the IPost＋inhibitor groups（IPost＋W-146 group and IPost＋PD98059 group） showed that in the first 15 min of re-perfusion addition of W-146 and PD98059 reversed all changes observed in the IPost group and eliminated the IPost protection by increasing infarction