一类新的调控心律失常发生的靶点——microRNAsAnovel-药学学报.PDF

药学学报 Acta Pharmaceutica Sinica 2009, 44 (8) : 833837 ·833 · 一类新的调控心律失常发生的靶点 microRNAs 蔡本志, 吕延杰, 杨宝峰* (哈尔滨医科大学药理学教研室, 黑龙江省生物医 重点实验室－省部共建国家重点实验室培育基地, 哈尔滨医科大学心血管药物研究所, 黑龙江 哈尔滨 150081) 摘要: microRNAs (miRNAs) 是一类长约22 个核苷酸的非编码小分子RNA, 通过与靶蛋白mRNA 3 端非编 码区的不完全互补结合, 抑制靶 mRNA 转录后的表达。最近大量研究显示 miRNA 在心脏病理、生理过程中发 挥重要的调控作用, 尤其与心律失常的发生、发展密切相关。miRNA 过度上调或下调可引起离子通道蛋白表达 紊乱, 致离子通道平衡失调, 诱发心律失常。本文将从与心律失常发生相关的心肌缺血、心肌肥厚和糖尿病心肌 病三个方面就miRNA 在心律失常中的调控作用作一综述。旨在揭示miRNA 变化在心脏疾病发生、发展中的重 要地位, 并探讨以miRNA 为靶点防治心律失常以及心源性猝死的可行性。 关键词: microRNA; 心律失常; mRNA; 离子通道 中图分类号: R963 文献标识码:A 文章编号: 05 13-4870 (2009) 08-0833-05 A novel target for the regulation of cardiac arrhythmias ―microRNAs * CAI Ben-zhi, L Yan-ji e, YANG Bao-feng (Depa rtment of Pharmacology, State-p rovince Key Laboratories of Biomedicine Pharmaceutics of China, Cardiovascular Drug Institute, Harbin M edical University, Harbin 150081, China) Abstract: microRNAs are one kind of endogenous no-encoding RNA with about 22 nucleotides in length, and inhibited the translation of mRNAs by partially complementary binding to the 3 UTR of target mRNAs in the post-transcriptional level. Recent research shows that miRNAs function in the physiological and pathological processes of heart, especially involved in the occurrence and progress of arrhythmias. Abnormal miRNAs alters the protein expression of ion channels, causes the cardiac dysfunction, and triggers heart arrhythmias. The article summarized recent advances about ro