抄録
A cyanobacterial toxin, microcystin-LR (MCLR), is a potent inhibitor of protein phosphatase that disrupts cytoskeleton network in hepatocytes. Conventional transmission electron and immunoelectron microscopic studies were conducted in the liver from mice that received a single dose of MCLR and were sacrificed at 24 hours after dosing. The two types of death of hepatocytes, necrosis and apoptosis, were observed concomitantly, and the hepatic injuries, therefore, could be classified as a class of mixed apoptotic and oncotic necrosis according to the recommended criterion by the Society of Toxicologic Pathologists. Apoptotic hepatocytes were characterized by ballooning with numerous intracytoplasmic vacuoles in addition to the common features of apoptotic cells referred in the literatures. In non-parenchymal cells, significant changes indicating microcirculatory alterations and inflammatory reactions included activation of endothelial cells and Kupffer cells, widening of sinusoidal endothelial fenestrae, apoptosis of endothelial cells, accumulation of platelets and polymorphonuclear neutrophils, and fibrin deposition. Pre-embedding immunoelectron microscopy with biotinylated anti-microcystin antibody demonstrated that MCLR was heterogeneously apparent in the cytoplasm of hepatocytes and strong immunoreactivity was evident in apoptotic cell/bodies. In non-parenchymal cells, there were no positive reactions except for phagocytic apoptotic bodies in Kupffer cells. These results suggest that liver damages induced by MCLR are ascribed to primary cytotoxic effects of the toxin localized in hepatocytes and secondary microcirculatory alterations and inflammatory reactions involved non-parenchymal cells.
