基于microRNA及mtDNA相关性阐述活血化痰中药防御心肌缺血再灌注损伤分子机制.docVIP

基于microRNA及mtDNA相关性阐述活血化痰中药防御心肌缺血再灌注损伤分子机制 　　[摘要]大量基础和临床研究显示活血化痰中药通过调节脂质代谢防治心肌缺血再灌注损伤（myocardial ischemia reperfusion injury，MIRI），然其机制尚不十分清晰。经研究线粒体DNA，microRNAs以及脂质代谢参与MIRI整个过程且影响预后，线粒体DNA mtDNA突变是引起心肌缺血和再灌注心肌细胞损伤的首要因素，microRNAs通过表达下降或过表达调控相关基因加重或减轻MIRI损伤，而作为胆固醇转运关键调节器的miR-33通过位于线粒体上CROT，PGC-1α，AMPK等相关基因而调控脂质代谢，然同mtDNA和microRNAs的相关性研究却较之为少。因此深入研究miR-33同mtDNA，MIRI的相关性，探析活血化痰中药是否靶标miR-33调节脂质代谢，引起mtDNA突变或缺失对于防治MIRI有着重要意义 [关键词] 冠心病； 线粒体； microRNA； 脂质代谢 [Abstract] A large number of basic and clinical studies have shown that the Chinese herbs with promoting blood circulation and resolving phlegm effects could prevent and treat myocardial ischemia-reperfusion injury（MIRI） by regulating lipid metabolism. But its mechanism is not yet clear. The studies show that mitochondrial DNA （mtDNA）， microRNAs and lipid metabolism participate in the whole process of MIRI and affect the prognosis. mtDNA mutation is the primary factor to cause myocardial ischemia and reperfusion myocardial cell damage. microRNAs aggravate or reduce MIRI injury by down-regulating or up-regulating related genes expression， while miR-33， as a key regulator of cholesterol transport， regulates lipid metabolism through CROT， PGC-1α， AMPK and other genes located in the mitochondria. There are less studies on correlation between miR-33 and mtDNA， microRNAs. Therefore， further studies on the correlation between miR-33 and mtDNA， microRNAs， as well as the discussions on whether the traditional Chinese medicine （TCM） with promoting blood circulation and resolving phlegm effects could target miR-33 to regulate lipid metabolism and inducemt DNA mutations or deletions， would have important significance for the prevention and treatment of MIRI. [Key words] coronary heart disease； mitochondria； microRNA； lipid metabolism 心肌缺血再灌注?p伤（myocardial ischemia reperfution injury，MIRI）是引起静脉溶栓、经皮冠状动脉介入术、冠状动脉旁路移植术后心律失常、心肌舒缩功能降低、能量代谢障碍、细胞凋亡的首要病理因素之一[1]。近些年，中药以其独特多途径多靶点的协同疗效广泛应用于MIRI的防治，大量研究表明中药通过减少氧化应激、改善能量代谢、防止细胞凋亡、抑制钙超载