中文摘要：

内质网应激（endoplasmic reticulum stress,ERS）是细胞对环境改变的适应性反应,但过度ERS可诱导细胞凋亡。C/EBP同源蛋白（C/EBP homologous protein,CHOP）是ERS相关凋亡途径中重要的信号分子。本实验旨在探讨CHOP介导的ERS相关凋亡途径在大鼠腹主动脉狭窄致高血压心肌肥厚发生、发展中的作用。健康雄性Wistar大鼠85只,随机分为模型组（n=45）和对照组（n=40）,模型组行腹主动脉狭窄术,对照组仅分离腹主动脉不行狭窄术,分别于术后1d、3d、7d、14d、28d时观察各组血流动力学变化,测定全心重/体重比（HW/BW）和左心室重/体重比（LVW/BW）,RT-PCR技术检测左心室心肌组织ERS相关分子葡萄糖调节蛋白78（glucose-regulated protein78,GRP78）、钙网蛋白（calreticulin,CRT）和CHOPmRNA表达变化,Western blot分析GRP78、CRT、CHOP,以及凋亡相关蛋白Bax和Bcl-2表达变化。结果显示,腹主动脉狭窄可诱导大鼠心肌肥厚,与对照组比较,术后7d模型组大鼠血压升高,心功能代偿性增加,HW/BW和LVW/BW显著增加。模型组内质网分子伴侣CRTmRNA表达于术后1d即发生显著上调,较对照组增加136%（P〈0.01）,而蛋白在术后7d开始出现显著变化,较对照组升高69.2%（P〈0.01）;GRP78基因和蛋白表达均于术后7d显著增加,分别较对照组增加20%和186%（均P〈0.01）,在此后观察期间内CRT和GRP78mRNA和蛋白均持续高水平表达。相关分析显示左心室内压最大上升速率（＋dp/dtmax）分别与CRT蛋白表达（r=0.780,P〈0.01）和GRP78蛋白表达（r=0.694,P〈0.01）显著正相关。长期ERS（14d）可触发CHOP凋亡途径,模型组大鼠心肌组织CHOP mRNA和蛋白表达均于术后14d显著上调,分别较对照组增加22.2%和76.0%（均P〈0.01）,同时促凋亡蛋白Bax表达增加（较对照组增加41.1%,P〈0.01）,而抗凋亡蛋白Bcl-2表达降低（较对照组降低25.5%,P〈0.01）;相关分析显示CHOP蛋白表达与Bax表达正相?

英文摘要：

Endoplasrnic reticulum stress （ERS） is an adaptive process in response to circumstantial changes, but excessive and/or prolonged ERS can induce cell apoptosis. C/EBP homologous protein （CHOP） is a very important marker participating in ERS- associated cell apoptosis, while the role of the myocyte apoptosis induced by CHOP remains unclear in the development of hypertrophy.The present study aimed to investigate the effect of CHOP-mediated ERS-associated apoptosis on myocardial hypertrophy induced by abdominal aortic constriction in rats. Healthy male Wistar rats were randomly divided into model group （n=45） and control group （n=40）. The rats in model group received abdominal aortic constriction. Hemodynamic changes, whole heart weight/body weight （HW/ BW） and left ventricular weight/body weight （LVW/BW） were measured on 1 d, 3 d, 7 d, 14 d and 28 d after surgery, respectively. The mRNA expression of glucose-regulated protein 78 （GRP78）, calreticulin （CRT） and CHOP, which are important markers of ERS, were detected by RT-PCR, and Western blot was used to assess the protein level of GRP78, CRT, CHOP, and apoptosis-associated proteins, Bax and Bcl-2. The results obtained were as follows. Compared with control group, the blood pressure, LVW/BW, and HW/BW of rats in model group increased significantly and cardiac function enhanced compensatively on 7 d after surgery, and increased progressively during the experiment. As early as 1 d after surgery, the mRNA level of CRT in model group increased by 136% （P〈0.01） compared with control, while the protein expression increased by 69.2% on 7 d after surgery （P〈0.01）. Both mRNA and protein expression of GRP78 increased by 20% and 186% （P〈0.01） respectively on 7 d after surgery, and the expression sustained high level during the experiment afterwards. Correlation analysis indicated a positive correlation between ＋dp/dtmax and CRT protein expression （r=-0.780, P〈0.01） as well as GRP78 protein expression （r=0.694, P〈0.0