解偶联剂(FCCP)与氰化钾(KCN)对禁食大鼠肝细胞酮体代谢的影响

THE EFFECT OF UNCOUPLER (FCCP) AND POTASSIUM CYANIDE ON THE KETOBODY PRODUCTON IN THE ISOLATED HEPATOCYTES OF FASTED RATS

目的：研究解偶联剂（ＦＣＣＰ）和呼吸链阻断剂氰化钾（ＫＣＮ）对禁食大鼠肝细胞酮体代谢的影响。方法：使用胶原酶法分离大鼠肝细胞，然后分６组比较ＦＣＣＰ和ＫＣＮ对β羟丁酸（ＢＯＨＢ）和乙酰乙酸（ＡＣＡＣ）以及ＡＴＰ水平的影响。结果：单独使用ＦＣＣＰ和ＫＣＮ可使肝细胞损伤而酮体生成减少，加入丙酮酸后，ＦＣＣＰ使酮体生成（Ｐ＞００５），ＢＯＨＢ／ＡＣＡＣ比率与对照组无显著差别（Ｐ＞００５），而ＡＴＰ则明显减少（Ｐ＜００１）；ＫＣＮ则使酮体生成增加（Ｐ＜０００１），且ＢＯＨＢ／ＡＣＡＣ比率显著增加（Ｐ＜００１），ＡＴＰ也显著减少（Ｐ＜０００１）。结论：ＦＣＣＰ和ＫＣＮ均为强力的ＡＴＰ合成抑制剂，但作用机制不同，加入丙酮酸后ＦＣＣ使ＮＡＤＨ／ＮＡＤ比率降低，以ＡＣＡＣ为主；ＫＣＮ则使ＮＡＤＨ／ＮＡＤ比率增加，故以ＢＯＨＢ为主。

Objective: To study the effects of Uncoupler( Carbonyl cyanide p trifluoro methoxyphenylhydrazone FCCP)and respiratory chain blocker,potassium cyanide (KCN) on the ketobody production by the isolated hepatocytes of the fasted rats Methods: Hepatocytes were isolated from adult male wistar rats(280￣200g)fasted for 16 hours by perfusing collagenase The effects of FCCP changed beta hydroxybutyric acid(BOHB), acetocetic acid (ACAC) and ATP levels, comparing with that of KCN in different groups Results: FCCP or KCN used alone, caused the decreased ketobody production as a result of hepatocytes damaged When pyruvate was added into culture medium, FCCP enabled to bring about the production of ketobody ( P <0 05)and the ratio of BOHB/ACAC( P > 0 05) near to the level of controled group, but ATP level was much more significantly decreased( P <0 001) KCN could markedly increase ketobody( P <0 01) and the ratio of BOHB/ACAC( P <0 01)and deplete ATP level( P <0 001) Conclusion: FCCP and KCN were powerful inhibitors of ATP production with different ways When pyruvate was added, FCCP decrease the ratio of NADH/NAD and ACAC was prevalent in ketobody; KCN increased the ratio of NADH/NAD and BOHB was much more than ACAC