心脏microRNAs在丙泊酚所致心肌抑制中的作用及机制研究

项目名称： 心脏microRNAs在丙泊酚所致心肌抑制中的作用及机制研究

项目编号： No.81500178

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 姚优修

作者单位： 北京大学

项目金额： 18万元

中文摘要： 丙泊酚对心血管系统的抑制作用是临床麻醉中普遍关注的热点问题。虽然有研究提示丙泊酚可能通过影响L-型钙通道和β受体信号通路导致心肌抑制，但其上游作用机制尚不明确。我们在前期预实验中发现，丙泊酚可引起let-7e等microRNA的表达明显改变，鉴于microRNA可与靶位点mRNA 3’非编码区结合，从而调控基因表达，故推测microRNA的这种表达改变可能会引起L-型钙通道和β受体信号通路变化。本课题通过大鼠静脉输注丙泊酚、新生大鼠心肌细胞培养和大鼠在体慢病毒载体转染模型，采用microRNA 芯片、qRT-PCR、Westernblot等方法，从分子、细胞、组织以及动物整体水平等多方面研究丙泊酚引起的心脏microRNAs的表达变化。 在此基础上，进一步探讨丙泊酚是否通过心脏microRNA介导影响L-型钙通道和β受体信号通路变化，为揭示丙泊酚心肌抑制作用的分子机制提供实验依据。

中文关键词： 麻醉；丙泊酚；微小RNA；心脏

英文摘要： Propofol-induced cardiovascular depression is a widely concerned issue in clinical anesthesia. Although studies suggest that propofol may influence L-type calcium channels and β receptor signaling pathways leading to myocardial depression, the upstream molecular mechanism, however, is still poorly understood. In our preliminary experiments, we found that propofol can cause significant changes in microRNA let-7e expression, etc.. MicroRNAs exert their repressive functions by binding to sequences in the 3' untranslational region of target mRNAs, thereby regulating gene expression. Therefore, we hypothesized that the altered microRNA expression might cause L-type calcium channels and β receptor signaling changes. This study is designed to investigate the propofol-induced cardiac microRNAs expression changes using microRNA array. In addition, we will further explore whether propofol-induced microRNAs can affect L-type calcium channels and β receptor signaling changes by using cultured neonatal rat cardiomyocytes and in vivo lentiviral vector transfection rat models, and by qRT-PCR, Westernblot. The results of the present study may provide experimental evidence and a new theoretical basis for further elucidating the upstream molecular mechanisms of propofol-induced myocardial depression.

英文关键词： anesthesia;propofol;microRNA;heart