【摘要】 用四氯化碳引起小白鼠中毒性肝炎,同时每天注射I-677 100毫克/公斤,对一次中毒的急性肝损伤或反复中毒5次疗程15天的亚急性肝损伤都有明显的降低血清谷丙转氨酶(GPT)作用,病理切片证明肝细胞变性和坏死程度都较对照组为轻。在四氯化碳中毒连续8周引起肝硬化的过程中,每日给予I-677,除血清胆红素降低外,对其他肝功能、肝胶元含量和肝组织切片检查,均无明显影响。I-677作用机理的研究发见,血清GPT的降低与肝组织GPT的降低有关,同时给予L-赖氨酸,不能对抗其降酶作用。I-677与肝匀浆或高GPT血清在体外培养,未观察到对GPT的直接抑制作用。与GPT抑制剂氨氧醋酸比较,后者在体外有明显抑制GPT作用而体内则无降酶效果。大白鼠每日灌胃I-677 80～320毫克/公斤(临床剂量的8～32倍),连续11周,可引起血清白蛋白的降低和丙球蛋白的升高。用氚标记赖氨酸对蛋白的掺入试验也证明,大剂量I-677对肝脏的蛋白质合成和脂肪转运有一定影响,但这种作用可被赖氨酸所对抗。更多还原

【Abstract】 Toxic hepatitis was induced with carbon tetrachloride in mice. L-4-oxalysine （I-677） l00mg/kg injected daily has been proved to be effective in lowering the serum glutamic-pyruvate transaminase （SGPT） level in both aoute and subacute liver injuries. Pathological examinations also showed that the degeneration and necrosis of liver cells were protected by the administration of I-677. In the course of inducing experimental liver oirrhosis with CCl₄, I-677 administered for 8 weeks affected neither liver function besides a lowering of serum bilirubin, nor liver collagen content and histological appearance. The mechanism of serum GPT-lowering was found to be a lowering of hepatic enzyme activity. No direct inhibition on the activity of both liver and serum GPT was observed in vitro. The transaminase-lowering effect of I-677 could not be antagonized by simultaneous administrations of L-lysine. Amino-oxyacetic acid, a GPT inhibitor, showed potent inhibition on the GPT activity in vitro, but not in vivo. Large doses of I-677 （8-32 times the clinical dose） for 11 weeks in rats induced a lowering of serum albumin, a decrease of incorporation of ³H-lysine into serum protein, and an increase of the lipid of liver. This revealed that albumin synthesis and lipid transport function of liver were inhibited by I-677, but this effect could be antagonized by L-lysine.更多还原