Schultz-Hector S, Balz K
GSF-Institut für Strahlenbiologie, Neuherberg, Federal Republic of Germany.
Lab Invest. 1994 Aug;71(2):252-60.
There is general agreement that radiation effects on capillary endothelial cells are a leading event in the pathogenesis of late effects of radiation in normal tissues. The mechanism of microvascular involvement however is unclear. In the myocardium, there is not only a decrease in capillary number, but a focal loss of endothelial alkaline phosphatase. The present study addresses the question of whether radiation-induced alkaline phosphatase loss is due to cell death or to modification of cell function and ultrastructure.
The time course of ultrastructural changes underlying endothelial alkaline phosphatase loss and development of myocardial degeneration was studied in two strains of rat, that differ in latent time of clinical radiation-induced cardiomyopathy.
In both strains of rat, development of ultrastructural damage in cardiomyocytes was preceded by a focal loss of endothelial alkaline phosphatase reactivity. The absence of enzyme reaction product was neither due to endothelial cell loss, nor to a depletion in enzyme-bearing cytotoxic vesicles. The endothelial cell/pericyte relationship was also unchanged. Within enzyme-negative areas, there was an increased number of enlarged endothelial cells and of lymphocyte adherence to endothelial cells, which was then followed by endothelial cell rupture and extravasation of blood cells. In Wistar rats, enzyme loss started at 25 days after 20 Gy and reached its maximum extent by 90 days. In Sprague-Dawley rats, which show a significantly higher pre-irradiation enzyme reactivity, the onset of alkaline phosphatase loss and associated alterations was delayed by about 30 days and was significantly less extensive.
Radiation-induced endothelial alkaline phosphatase loss is unrelated to cell death in mitosis, but nonetheless it is relevant for the development of ultimate clinical heart failure.
人们普遍认为，辐射对毛细血管内皮细胞的影响是正常组织辐射晚期效应发病机制中的主要事件。然而，微血管受累的机制尚不清楚。在心肌中，不仅毛细血管数量减少，而且内皮碱性磷酸酶出现局灶性缺失。本研究探讨辐射诱导的碱性磷酸酶缺失是由于细胞死亡还是细胞功能及超微结构改变所致。
在两种大鼠品系中研究了内皮碱性磷酸酶缺失及心肌变性发展过程中超微结构变化的时间进程，这两种品系在临床辐射诱导的心肌病潜伏期方面存在差异。
在两种大鼠品系中，心肌细胞超微结构损伤的发展之前均有内皮碱性磷酸酶反应性的局灶性缺失。酶反应产物的缺失既不是由于内皮细胞丢失，也不是由于含酶细胞毒性小泡的消耗。内皮细胞/周细胞关系也未改变。在酶阴性区域，内皮细胞肿大以及淋巴细胞黏附于内皮细胞的数量增加，随后是内皮细胞破裂和血细胞外渗。在Wistar大鼠中，20 Gy照射后25天开始出现酶缺失，90天时达到最大程度。在Sprague-Dawley大鼠中，其照射前酶反应性显著更高，碱性磷酸酶缺失及相关改变的起始延迟约30天，且程度明显较轻。
辐射诱导的内皮碱性磷酸酶缺失与有丝分裂中的细胞死亡无关，但与最终临床心力衰竭的发展相关。
