半胱氨酸预防FCCP所致体外大鼠肝细胞损伤研究  

The Study of Cysteine in Prevention of the Isolated Rat Hepatocytes from FCCP

作　　者：张孝山[1] 

机构地区：[1]天津市传染病医院

出　　处：《生物化学杂志》1996年第1期99-103,共5页

摘　　要：ＦＣＣＰ作为质子传递型氧化磷酸化解偶联剂，是一种强力的ＡＴＰ合成抑制剂。８０μｍｏｌ／Ｌ的ＦＣＣＰ可在数分钟内使细胞内的ＡＴＰ耗竭。半胱氨酸可使ＦＣＣＰ引起的ＡＴＰ，氧消耗量和乳酸脱氢酶逸出率等改变恢复正常。半胱氨酸对ＦＣＣＰ的解毒作用是特异的和与剂量有关，而其他含巯基剂如：还原型谷胱甘肽和二硫苏糖醇（ＤＴＴ）则不能干扰ＦＣＣＰ对细胞线粒体功能的影响。Carbonyl cyanide p-trifluoro-methoxyphenylhydrazone (FCCP), a protonophric uncoupler of oxidative phosphorylation is a potent metabolic inhibitor to deplete ATP level. 80 μmol/L of FCCP was able to decrease ATP concentration within a few minutes of incubation. Cysteine was able to get rid of effect of FCCP, in which the ATP level returned to normal, and all increased O_2 consumption by treatment with FCCP plus pyruvate and decreased O_2 consumption by treatment with FCCP alone were also returned to normal range. Although hepatocytes were preincubated with 80 μmol/ L of FCCP for ten and twenty minutes, 10 mmol/L of cysteine added did recover ATP level to normal within another 20 to 30 minutes of incubation period. In addition, LDH leakage in incubation medium of hepatocytes treated with FCCP plus cysteine was similar to normal control. Trypan blue exclusion showed that the result agreed with that of level and leakages of cytoplasm enzyme,and cell blebbing was not produced. The detoxicative effect of cysteine to FCCP was specific and dose-dependent,in which 5 mmol/L of cysteine might counteract with 80 μmol/L of FCCP. On the other hand ,cysteine could completely reverse the inhibitive effect produced by FCCP on uncoupling of oxidative phosphorylation and mitochondrial function was recovered. In general, with cysteine added, the effects of FCCP disappeared, but other thio group containing (-SH) reagents such as reduced glutathione (GSH),dithiothreitol(DTT) and methionine did not counteract the effect of FCCP.

关 键 词：半胱氨酸 FCCP 肝细胞损伤 药理学 解毒作用 

分 类 号：R977.4[医药卫生—药品] R575.1[医药卫生—药学]