CDK9及其抑制剂在心肌肥大中的作用机制研究

Study on the Mechanisms of CDK9 and Its Inhibitors in Myocardial Hypertrophy

心肌肥大的特征是分化的心肌细胞体积的增加,在分子水平上,心肌肥大与细胞的转录和翻译密切相关。研究发现细胞周期蛋白依赖性激酶9(CDK9)与心肌肥大相关。CDK9作用于磷酸化RNA聚合酶Ⅱ的C端结构域,从而刺激心肌细胞分化中转录的延长阶段。长期激活的CDK9不仅可引起心肌细胞增大,还可能导致心力衰竭,加重患者病情。针对CDK9的抑制剂如5,6-二氯-1-β-D-呋喃核糖苯并咪唑、Flavopiridol、Roscovitine等可抑制心肌肥大,了解这些化合物的作用机制以及与CDK9的结合方式可为心肌肥大的治疗提供提供帮助。

Myocardial hypertrophy is characterized by volume increase of differentiation of cardiomyocytes,on the molecular level,myocardial hypertrophy has a very close relationship with the transcription and translation of cells. The study found that cyclin dependent kinase 9（ CDK9） was associated with myocardial hypertrophy. CDK9 acts on the phosphorylation of RNA polymeraseⅡC terminal domain structure,thus stimulating the extension of transcription in myocardial cell differentiation stage. Long-term activation of CDK9 not only can cause myocardial cells to increase,but also can lead to heart failure and aggravate the patient＇ s condition. CDK9 inhibitors such as 5,6-dichloro-1-beta-D-furribose benzimidazole,Flavopiridol,Roscovitine can inhibit myocardial hypertrophy,and understanding the action mechanism of these compounds and the ways of combining with CDK9 can provide help for the treatment of myocardial hypertrophy.