Glees P, Spoerri P E
Arzneimittelforschung. 1975 Oct;25(10):1543-8.
Three batches of senile guinea pigs were injected i.m. daily with 80 mg/kg, 50 mg/kg, or 30 mg/kg up to 10 weeks. With the dosage employed neurons of the central nervous system showed in all animals a significant reduction of lipofuscin pigment. A characteristic type of vacuolisation of the pigment is a preliminary sign of its reduction in size and quantity. Residuals of lipofuscin can be detected in astrocytes and in greater quantity in microglia cells and cells of the capillary wall. The dissolution of lipofuscin is not only found in the CNS but also in the myocardium and in the liver. In the latter organs the removal of pigment is carried out by phagocytes towards capillaries. The actual uptake of phagocytes is believed to occur by the process of exocytosis and pinocytosis. A destruction or an invasion of neurons by microglia has not been observed. Lipofuscin removal at a very small rate by microglia cells appears to occur normally in the ageing animal, but is greatly enhanced by centrophenoxin. Cessation of drug application does not stop the process of removal at once and the process continues as far as we can judge by our experiments for several weeks without further drug application. Even 30 mg/kg per day were found to be sufficient to initiate and sustain lipofuscin removal.
将三组老年豚鼠每日肌肉注射80毫克/千克、50毫克/千克或30毫克/千克,持续10周。在所使用的剂量下,所有动物的中枢神经系统神经元中的脂褐素色素均显著减少。色素空泡化的一种特征类型是其大小和数量减少的初步迹象。脂褐素的残余物可在星形胶质细胞中检测到,在小胶质细胞和毛细血管壁细胞中含量更多。脂褐素的溶解不仅在中枢神经系统中发现,在心肌和肝脏中也有发现。在后者的器官中,色素的清除是由吞噬细胞向毛细血管进行的。吞噬细胞的实际摄取被认为是通过胞吐作用和胞饮作用进行的。未观察到小胶质细胞对神经元的破坏或侵袭。在衰老动物中,小胶质细胞以非常低的速率清除脂褐素似乎是正常的,但被氯酯醒大大增强。停止给药并不会立即停止清除过程,就我们的实验判断,在没有进一步给药的情况下,这个过程会持续数周。甚至发现每天30毫克/千克就足以启动并维持脂褐素的清除。