Apoptosis in the conduction system of the heart in the senscence accelerated mouse (SAM)

研究背景和目的心脏传导阻滞等心脏疾病常发生于老年患者，但其发病机制尚不清楚。加速衰老小鼠（SAM）是一种新型的小鼠加速衰老模型。为了阐明衰老心脏传导系统中心肌细胞的丢失，用常规光镜和透射电镜观察了SAM的房室传导组织。同时应用光镜和电镜原位末端标记技术（TUNEL）检测dUTP的表达。结果LM偶见心肌细胞萎缩，核固缩，但不常见。电镜观察显示心肌细胞偶发性发生多种退行性变化，表现为肌原纤维和中间丝的解体、肌浆网增大、胞浆内空泡、曲线膜形成和罕见的质膜破坏。在一些退化的心肌细胞中，核染色质在明显保存的核膜下浓缩并边缘化。在心包中，一些巨噬细胞似乎吞噬了变性的心肌细胞，并包括一些残留体，但没有炎性细胞浸润。房室传导组织心肌细胞变性较工作心肌细胞变性多。在房室传导组织中偶见光镜和电镜TUNEL阳性细胞。结论SAM心脏房室传导系统心肌细胞的死亡可能是由传导细胞衰老过程中的凋亡所引起的。

*Background and Purpose* Cardiac disorders such as heart block often develop in aged patients, but the pathogenesis remains unexplained. The senescence accelerated mouse (SAM) is a novel murine model of accelerated senescence. To clarify loss of cardiocytes in the conduction system of aging heart, atrioventricular (AV) conducting tissue from SAM was examined with conventional light (LM) and transmission electron microscopy (EM). Both of light ane electron microscopic in situnick end labeling of dUTP (TUNEL) was also applied. *Results* LM showed atrophic myocardial cells with shrunk nuclei occasionally but not very often. EM revealed that cardiocytes sporadically underwent a variety of degenerative processes, which were characterized by disorganization of myofibrils and intermediate filaments, enlarged sarcoplasmic reticulum, intracytoplasmic vacuoles, curvilinear membranous formation, and rare disruptions of the plasma membrane. Nuclear chromatin was condensed and marginated beneath apparently preserved nuclear membrane in some degenerated cardiocytes. In the interstitium, some macrophages appeared to have phagocytosed degenerated cardiocytes and included some residual bodies, but there was no infiltration of inflammatory cells. Cardiocytes degenerated more often in AV conducting tissue than in working myocardium. Furthermore, light and electron microscopic TUNEL-positive cardiocytes were seen occasionally in AV conducting tissu. *Conclusion* It is concluded that myocardial cell death in AV conduction system of SAM hearts may be induced by apoptosis which is programd in aging process of conducting cardiocytes.