容量超负荷诱导心力衰竭研究进展

Research progress of volume-overload-induced heart failure

容量超负荷动物模型制作通常分为低压力型和高压力型两类。低压力型通常采用二尖瓣反流模型;高压力型通常采用主动脉反流和主动脉腔静脉瘘模型。容量超负荷和细胞外基质相关,会引起左室细胞外基质重构,进而导致进展性的结构和功能性的左室重构,引发细胞外基质的降解与更新的不平衡。肥大细胞、心肌纤维化细胞及活性氧自由基和容量超负荷诱导心力衰竭的过程中发挥着重要的作用。本文总结了容量超负荷和压力超负荷诱导心力衰竭在机制方面的差异,揭示了肥大相关信号在两类超负荷心脏重构中的差异,并初步提出了钙调神经磷酸酶(CaN)和蛋白激酶B(Akt)信号通路可能分别是针对两类超负荷精准化治疗的靶点。未来对其上下游调控因子在两类超负荷心脏重构中的调控差异,尚需进行更深入的研究。

The volume overload animal models can be divided into low pressure and high pressure models.Mitral regurgitation is often used in low pressure models,whereas aortic regurgitation and aortocaval fistula are often used in high pressure models.Volume overload is related to extracellular matrix(ECM)and might cause left ventricular ECM remodeling,inducing progressively structural and functional left ventricular remodeling and ECM degradation and turnover imbalance.Mast cell,cardiac fibroblast,and reactive oxygen species play important roles in the process of volume overload in heart failure.In this review,the difference between the mechanisms of volume overload and pressure overload in heart failure,and the difference between hypertrophy-related signals in these two kinds of overload cardiac remodeling were reviewed.The review suggests that the calcineurin(CaN)and protein kinase B(Akt)may become the target in the treatment of volume overload and pressure overload in heart failure.In the future,further studies are needed to unveil the difference in the regulation of upstream and downstream regulatory factors in two kinds of overload cardiac remodeling.