运动性心肌肥厚中PKC信号通路研究进展

摘要

心肌肥厚是心脏受到刺激后的一种代偿反应。心肌的生理性肥厚可提高心脏机能，但病理性肥厚则会引起心血管疾病心律失常发病和死亡，亦是运动员发生猝死的原因之一。明确运动性心肌肥厚的机制，可为保护运动员心脏提供理论依据。目前为止，形成心肌肥厚的信号通路包括PKC、蛋白激酶B（Akt）、钙调神经磷酸酶（CaM）、丝裂原活化蛋白激酶MAPK、酪氨酸激酶受体gp130／STAT、牵拉敏感离子通道以及细胞骨架等。其中PKC途径是调控心肌细胞的生长、分化以及肥厚的过程中信号转导通路的关键环节。心肌细胞可通过Gq／PLC／Ca2＋／PKC、PKC／MAPK、PKC／NF-κB等相关途径促使活化晚期反应基因使心肌肥厚。在运动过程中，形成的生理性肥厚主要通过AkffmTOR途径。心肌细胞的机械牵拉亦可以通过PKC信号传导促使肥厚。PKC包括13种亚型，各亚型对心脏的作用不一。PKCa对多次运动后心肌有保护作用；PKCβ1对心肌可能有保护作用，B2则是相反的作用；PKC8有利于心肌细胞的适应；PKCs对心肌的保护作用亦有可能有相反的作用；PKCζ促使心肌肥厚。%Myocardial hypertrophy is a compensatory response after the heart stimulation. Myocardial physio- logic hypertrophy can improve heart function, but pathological hypertrophy may cause cardiovascular disease as onset of arrhythmia and death, and also one of the causes of sudden death in athletes. The clearing mecha- nism of exercise -induced cardiac hypertrophy can provide a theoretical basis for the protection of athlete＇ s heart. So far, formation of myocardial hypertrophy signaling pathways includes PKC, protein kinase B （ Akt）, calcineurin （ CaM）, activation of the mitogen - activated protein kinase MAPK, tyrosine kinase re- ceptor gpl30/STAT, and the stretch of sensitive ion channels and cytoskeletal etc.. The PKC pathway is the regulation of myocardial cell growth, differentiation and hypertrophy in the process of signal transduction pathway of key links. Myocardial cells through Gq / PLC / Ca2＋ / PKC, PKC / MAPK, PKC / NF kappa B related pathways induce activation of late response gene to myocardial hypertrophy. In the process of move- ment, formation of physiological hypertrophy makes Akt / roTOR the pathway. Myocardial cells to mechanical stretch are also available through PKC signal transduction induce hypertrophy. The PKC includes 13 subtypes, and each subtype on cardiac function is a. PKCa repeatedly after exercise myocardial protective effect; PKC beta 1 on myocardial may have a protective role, and beta 2 is the opposite effect ; PKC Delta in favor of myocardial cell adaptation; PKC E on the myocardial protective effects also may have the opposite effect; PKC zeta induces myocardial hypertrophy.