乳大鼠心室肌培养细胞代替急性酶分离细胞用于起搏电流电生理研究的可行性探索

目的 探讨体外培养细胞代替急性酶分离细胞用于心室肌电生理研究的可行性.方法 采用膜片钳全细胞记录技术,对比分析心室肌细胞培养的不同时间与急性酶分离的心室肌细胞起搏电流间的电生理学差异.结果 短期的培养就会使细胞膜电容下降,各期培养细胞的膜电容小于急性酶分离细胞的膜电容[(56±7) pF,P＜0.05].4d后膜电容随着培养时间的延长有逐渐增大的趋势,但各期之间的膜电容差异无统计学意义(P＞0.05).各个培养时间段细胞的反转电位、电流密度、活化阈值、半最大激活膜电压(V0.5)等主要电生理指标之间差异无统计学意义(P＞0.05).结论 至少短期培养的乳大鼠心室肌细胞的起搏电流与急性酶分离细胞的起搏电流的主要电生理指标之间无明显差异,可以代替急性分离细胞应用于起搏电流的电生理研究.     

Pyroptosis in cardiovascular diseases: Pumping gasdermin on the fire

Pyroptosis is a form of programmed cell death associated with activation of inflammasomes and inflammatory caspases, proteolytic cleavage of gasdermin proteins (forming pores in the plasma membrane), and selective release of proinflammatory mediators. Induction of pyroptosis results in amplification of inflammation, contributing to the pathogenesis of chronic cardiovascular diseases such as atherosclerosis and diabetic cardiomyopathy, and acute cardiovascular events, such as thrombosis and myocardial infarction. While engagement of pyroptosis during sepsis-induced cardiomyopathy and septic shock is expected and well documented, we are just beginning to understand pyroptosis involvement in the pathogenesis of cardiovascular diseases with less defined inflammatory components, such as atrial fibrillation. Due to the danger that pyroptosis represents to cells within the cardiovascular system and the whole organism, multiple levels of pyroptosis regulation have evolved. Those include regulation of inflammasome priming, post-translational modifications of gasdermins, and cellular mechanisms for pore removal. While pyroptosis in macrophages is well characterized as a dramatic pro-inflammatory process, pyroptosis in other cell types within the cardiovascular system displays variable pathways and consequences. Furthermore, different cells and organs engage in local and distant crosstalk and exchange of pyroptosis triggers (oxidized mitochondrial DNA), mediators (IL-1β, S100A8/A9) and antagonists (IL-9). Development of genetic tools, such as Gasdermin D knockout animals, and small molecule inhibitors of pyroptosis will not only help us fully understand the role of pyroptosis in cardiovascular diseases but may result in novel therapeutic approaches inhibiting inflammation and progression of chronic cardiovascular diseases to reduce morbidity and mortality from acute cardiovascular events.