微小RNAs和长链非编码RNA对胃溃疡肝郁脾虚证线粒体低氧调控机制的研究

项目名称： 微小RNAs和长链非编码RNA对胃溃疡肝郁脾虚证线粒体低氧调控机制的研究

项目编号： No.81473596

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 郑小伟

作者单位： 浙江中医药大学

项目金额： 73万元

中文摘要： 胃溃疡是消化系统常见病，易并发出血、癌变等严重后果，西药治疗该病的有效性、安全性仍存在一些问题。中医药对胃溃疡肝郁脾虚证的认识符合现代医学身心疾病理论，验方柴黄胃溃宁对该病证临床疗效良好。前期实验利用2-DE联合质谱技术已找到该模型的差异性蛋白群，这与线粒体中低氧相关，柴黄胃溃宁能改善低氧状态。文献表明线粒体低氧状态与ROS、PHD、LDH-A、HIF-1α等蛋白相关，同时受多种微小RNAs/长链非编码RNAs的调控。本课题组认为胃溃疡肝郁脾虚证中可能存在某些微小RNAs/长链非编码RNAs对ROS、PHD、LDH-A、HIF-1α进行调控，导致差异性蛋白表达。因此，本课题组先筛选病证相关的微小RNAs，同时从差异性蛋白群/低氧相关蛋白/相关微小RNAs、长链非编码RNAs着手，联合GWAS等方法尝试探究胃溃疡肝郁脾虚证的本质和验方柴黄胃溃宁疗效的作用机制。

中文关键词： 肝郁脾虚证；微小RNAs；长链非编码RNA；低氧；柴黄胃溃宁

英文摘要： Abstract: Gastric ulcer is a common disease, easily complicated by bleeding, perforation, cancer and other serious consequences. As the main drugs used to treat gastric ulcer, proton pump inhibitors and the like have shortages in their effectiveness and safety. Understanding of Traditional Chinese Medicine with the gastric ulcer with syndrome of liver depression and spleen deficiency conforms the modern medical physical and mental illness theory,meanwhile the empirical formula,CHWKN has a fairly good effect on this syndromes clinically.By using two-dimensional gel electrophoresis combined with mass spectrometry technology in the previous study, the differential protein group in the model was found and turned out to be closely related to mitochondrial hypoxia regulatory mechanisms . According to the recent reports that hypoxia associated with ROS、PHD、LDH-A、HIF-1α, and many kinds of microRNAs/LncRNAs were involved in the generation of mitochondrial hypoxia regulatory mechanisms, and these representative proteins were regulated by some microRNAs/LncRNAs.So we assumed there might be microRNAs, LncRNAs losing the control of mitochondrial hypoxia state in the gastric ulcer with syndrome of liver depression and spleen deficiency,losing the control of these representative proteins,leading to the expression of differential protein. By screening the syndrome associated microRNAs first,while from the relevant differential protein group、these representative proteins and known regulatory microRNAs/LncRNAs, then combined with GWAS and other methods,we will explore the syndrome's essence and the therapeutic mechanism of CHWKN on the foundation of our previous study.

英文关键词： liver depression and spleen deficiency;microRNAs;LncRNA;hypoxia;CHWKN