内质网应激在肺动脉高压引起的右心肥厚与衰竭中的作用及分子机制

项目名称： 内质网应激在肺动脉高压引起的右心肥厚与衰竭中的作用及分子机制

项目编号： No.81200159

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学一处

项目作者： 左祥荣

作者单位： 南京医科大学

项目金额： 23万元

中文摘要： 肺动脉高压（PAH）治疗棘手、预后极差，已成为严重危害社会公众的卫生问题。右心室肥厚与衰竭是PAH患者生活质量低下和预后不良的决定因素。防治右心室肥厚与衰竭对治疗PAH治疗具有十分重要的临床意义。迄今为止，右心肥厚的机制尚不明确。大量研究表明内质网应激（ERS）是影响左心室心肌肥厚、衰竭发生发展的重要因素，抑制ERS可防治左心肥厚、衰竭。但有关ERS在PAH及其导致的右心肥厚、衰竭发生发展的作用和机制尚不明确。预实验中观察到ERS相关分子GRP78和CHOP出现在PAH大鼠肥厚的右心室心肌组织中。结合国内外相关研究，我们推测，ERS 及其介导的细胞凋亡是PAH右心肥厚、衰竭发生发展的早期决定因素。为证明这种假说，本实验应用分子生物学、SiRNA等技术，从整体和细胞两个层次，观察ERS及其介导的细胞凋亡通路对右心肥厚与衰竭的影响。预期研究结果将进一步深化对PAH右心肥厚、衰竭分子机制的认识。

中文关键词： 右心室重构；肺动脉高压；内质网应激；细胞凋亡；

英文摘要： Pulmonary arterial hypertension (PAH) is a severe disease characterized by an progressive increase in pulmonary vascular resistance and ultimately right ventricular hypertrophy and failure with limited therapeutic options and a dismal prognosis.It has become a serious public health problem. Right ventricular hypertrophy and failure are strong independent predictors of mortality and poor quality of life in patients with PAH. Prevention of right ventricular hypertrophy and failure for treatment of PAH has importantly clinical significance. So far,the mechanism of right ventricular hypertrophy is not clear. A large number of studies have demonstrated that endoplasmic reticulum stress (ERS) plays an important role in the development of left ventricular hypertrophy and failure. Thus, therapeutic interventions that inhibition of ERS will be promising strategies to prevent and treat left ventricular hypertrophy and failure. But the role and mechanism of ERS during the occurrence and development of right ventricular hypertrophy and failure caused by PAH is still not clear. Observation in preliminary experiments showed that the ERS related molecules GRP78 and CHOP expressed in PAH hypertrophic right ventricle organization. Upon on domestic and international researches, we hypothesized that ERS and its mediated apoptosis

英文关键词： Right ventricular remodeling；pulmonary arterial hypertension；endoplasmic reticulum stress；apoptosis；