中文摘要：

本文分别在整体实验和细胞培养条件下研究钙网蛋白（calreticulin，CRT）在低氧预处理（hypoxic preconditioning，HPC）延迟心肌保护中的表达及其信号转导机制。（1）整体实验时Wistar大鼠随机分为3组：假手术（sham）组、仅结扎冠状动脉的心肌缺血（myocardial infarction，MI）组和HPC后再结扎冠状动脉的HPC＋MI组，分别于术后24h、14d和28d观察HPC对缺血后心功能和梗死区、危险区面积的影响；采用Western blot检测CRT表达以及p38丝裂素活化蛋白激酶（p38mitogenactivated protein kinase，p38MAPK）、应激活化蛋白激酶（stress-activated protein kinase，SAPK）活性。（2）原代培养Sprague—Dawley乳鼠心肌细胞，随机分为6组：低氧，复氧（hypoxia／reoxygenation，H／R）组、HPC组、HPC＋H，R组、p38MAPK抑制剂SB203580＋HPC＋H／R（SB＋HPC＋H／R）组、SAPK抑制剂SP600125＋HPC＋H瓜（SP＋HPC＋H／R）组和正常对照组；采用台盼蓝排斥实验、乳酸脱氢酶（1actate dehydrogenase，LDH）活性检测及流式细胞仪检测各组细胞损伤情况；采用Western blot检测CRT表达及p38MAPK、SAPK的磷酸化水平。主要结果如下：（1）整体动物实验结果表明，HPC改善缺血对心肌左室压力最大上升，下降速度（＋dp／dtmax）的抑制，限制心肌梗死面积；HPC后CRT表达呈动态变化：术后24h时HPC＋MI组CRT表达增高106％（P〈0．05vsMI组），以危险区最为显著；14d至28d表达逐步降低。相关分析显示，术后24h时CRT表达量与心功能呈正相关（r=0．9867，P〈0．05），与梗死面积呈负相关（r=-0．9709，P〈0．05）。（2）细胞培养实验结果表明，HPC可减轻H／R诱导的心肌细胞LDH漏出，增加心肌细胞存活率，降低细胞凋亡；单纯HPC可诱导CRT表达轻度增加（222％，P〈0．05vs对照组），而损伤性H／R诱导CRT过表达（503％，P〈0．05vs对照组），HPC可降低H／R诱导CRT表达升

英文摘要：

Both in rive and cultured cardiomyocyte experiments were performed to investigate the alteration of expression of calreticulin （CRT） during the delayed cardioprotection induced by hypoxic preconditioning （HPC） and the intracellular signal transduction mechanisms of the alteration. （1） Wistar rats wore randomly divided into three groups： sham operation group （Sham）, myocardial infarction （iI） group induced by left coronary artery ligation and HPC＋MI group （4-hour HPC 24 h before iI）. Twenty-four hours, 14 d and 28 d after left coronary artery ligation, myocardial function, infarction size and the area at risk were measured. Western blot was used to detect the expression of CRT, the activity of p38 mitogen-activated protein kinase （MAPK） and stress-aedvated protein kinase （SAPK）. （2） Cultured cardiomyocytes from neonatal Sprague-Dawley （SD） rat were divided into six groups： hypoxia/ reoxygenation （H/R）, HPC, HPC＋H/R, p38 MAPK inhibitor SB203580＋HPC＋H/R （SB＋HPC＋H/R）, SAPK inhibitor SP600125＋HPC＋H/R （SP＋HPC＋H/R） and control. Survival rate and apoptosis rate of cardiomyocytes 6 h after H/R and activities of lactate dehydrogenase （LDH） in culture medium in each group were measured. Western blot was used to detect the expression of CRT and activities of p38 MAPK and SAPK. The results are as follows： （1） During in vivo experiment, compared with MI group, HPC significantly improved ＋dpldtmax and -dpldtmax, reduced infarction size and the area at risk. HPC dramatically changed the expression of CRT. CRT expression in HPC＋MI group was 206% of that in MI group （P〈0.05） 24 h after infarction, especially in the area at risk. However, 28 d after operation, the expression of CRT decreased by 57%. Correlation analysis indicated a positive correlation between CRT expression and myocardial function （r = 0.9867, P〈0.05）, and negative correlation between CRT expression and infarction size （r = -0.9709, P〈0.05）. （2） In cultu