醋氨酚大鼠肝细胞损伤及其机制的研究

醋氨酚(AAP)引起大鼠肝细胞膜损伤发生在肝细胞还原型谷胱甘肽(GSH)明显下降之后,提示GSH下降是AAP损伤肝细胞的原因之一。同步测定培养大鼠肝细胞GSH和胞浆自由钙离子浓度([Ca~(2+)f]c)的结果证明:加10mmol/L AAP培养2.5小时可引起GSH显著降低,[Ca~(2+)f]c明显升高。二巯基苏糖醇(DTT)5mmol/L可使加AAP后,细胞内GSH仍维持较高水平,[Ca~(2+)f]c升高几乎被完全拮抗。首次直接证明AAP所致的[Ca~(2+)f]c升高与GSH等巯基物质被消耗有关。

STUDY ON ACETAMINOPHEN-INDUCED RAT HEPATOCYTE INJURY AND ITS MECHANISM

We studied the acetaminophen (AAP)-induced primary cultured rat hepatocyte injury and its mecha-nism. The results showed that in monolayer-culture condition, AAP-induced lactic dehydrogenase (LDH)escape from the hepotocytes happened only when intracellular GSH was significantly reduced. This sug-gested the intracellular GSH depletion might be the causc of AAP-induced hepatocyte injury. By directdetermination of GSH and [Ca~(2+)f]c synchronously, we demonstrated for the first time that AAP couldcause GSH depletion and [Ca~(2+)f]c elevation in suspensionn-cultured hepatocytes. Dithiothreitol (DTT)could prevent the GSH depletion induced by AAP and completely antagonize the AAP-induced elevat-ion of [Ca~(2+)]c. It indicated that [Ca~(2+)f]c elevation could be the direct cause of AAP-induced rathepatocyte injury and that the elevation of [Ca~(2+)f]c might be linked with GSH depletion.