甲基异柳磷对大鼠游离肝细胞结构与功能影响及其在肝细胞中的代谢动力学研究

TOXICITY AND KINETICS OF MeISP IN ISOLATED RAT HEPATOCYTES

研究结果表明,甲基异柳磷(MeISP)在1.5mmol/L终浓度时对肝细胞有明显毒性,表现为膜通透性增高,细胞内丙氨酸氨基转移酶(ALT)、乳酸脱氢酶(LDH)、β-葡糖苷酸酶和酸性磷酸酶(AcP)漏出率增高,且ALT和LDH漏出率同MeISP间呈良好的剂量-效应关系;迅速耗损细胞内GSH;同MeISP共同温育30min的肝细胞膜发生明显的囊泡化;几乎完全抑制肝细胞蛋白质合成和糖异生功能.在15μmol/L终浓度下,在肝细胞内代谢迅速,符合代谢动力学一室模型(one—compartment model).

The influences of a new organophosphorous insecticide-MeISP on the structure and functions of the hepatocytes and the metabolic kinetics of MeISP were investigated using isolated rat hepatocyte suspension as an in vitro model. At the final concentration of 1.5 mmol/L, MeISP can (1) result in the increase of leakage of alanine aminotransferase (ALT) , la-ctate dehydrogenase (LDH) , β-glucuronidase and acid phosphatase(AcP) to the medium and a good dose-effect relationship; ( 2 ) give rise to obvious plasma membrane blebbing; (3) rapidly deplete the intracellular GSH and (4) almost completely inhibit the protein synthesis and gluco-neogenesis from sodium pyruvate. At the final concentration of 15μmol/L, the metabolism process of MeISP fits one-compartment model and MeISP is rapidly metabolized. The metabolism of MeISP in the hepatocytes with induced microsomal enzymes is accelerated.