四种半胱氨酸前体药对小鼠急性肝衰竭的保护作用

Protective effects of four L-cysteine prodrugs on acute liver failure in mice

目的 研究 2 甲基四氢噻唑 4 羧酸 (2 methylthiazolidine 4 carboxylicacid ,MTCA) ,四氢噻唑 4 羧酸 (thiazolidine 4 car boxylicacid ,TCA) ,N ,N 双乙酰胱氨酸 (N ,N diacetylcystine ,DAC) ,N 乙酰半胱氨酸 (N acetylcysteine ,AcCYS)对对乙酰氨基酚 (paracetamol,APAP)致急性肝衰竭 (acuteliverfailure ,ALF)的保护作用。 方法 小鼠ipAPAP 90 0mg·kg-1后 ,分别ipMTCA ,TCA ,DAC ,AcCYS ,监测小鼠血液化学和肝组织损害程度 ,监测小鼠凝血功能 ,高效液相色谱法监测血浆支链氨基酸和芳香族氨基酸 ,观察病死率。结果 4种半胱氨酸前体药均不同程度抑制血液化学的变化 ,减轻肝脏病理损害 ,改善凝血功能 ,纠正血浆氨基酸紊乱并降低病死率。结论 MTCA和DAC对APAP引起小鼠急性肝衰竭有明显保护作用 ,并优于Ac CYS 。

OBJECTIVE To study the protective action of 2 methylthiazolidine 4 carboxylic acid (MTCA),thiazolidine 4 carboxylic acid (TCA), N,N diacetylcystine (DAC) and N acetylcysteine (AcCYS) against acute liver failure induced by paracetamol APAP in mice.METHODS The mice were ip APAP 900 mg·kg -1 and then ip MTCA,TCA ,NAC and AcCYS respectively.The blood chemistry (sALT, sAST and TBil),aggregative function and mortality were examined.The concentration of amino acids in plasma were determined by HPLC.The damage of liver tissue was observed by light microscope.RESULTS Administration of four L cysteine prodrugs suppressed the elevation of serum ALT,AST,TBil levels, improved aggregative function and the histopathological changes in varying degree against APAP intoxicated mice.They also corrected the abnormal of plasma amino acid pattern and reduced mortality.CONCLUSION These results demonstrated that the protective effects of MTCA and DAC on APAP induced acute liver failure were superior to that of AcCYS.In contrast,TCA did not show any significant action.