4-氧和4-羟四甲基哌啶氮氧自由基及衍生物抗脂质过氧化作用研究

 目的:对6种四甲基哌啶氮氧自由基及衍生物(4-TEMPO)抗脂质过氧化作用进行了实验研究,为其进一步研究及应用于临床作为抗自由基损伤药物提供依据。方法:用Fe²⁺-VitC引发大鼠肝细胞膜、心肌细胞膜、肝线粒体的脂质过氧化,通过TAB比色法测定丙二醛(MDA)含量观测了4-TEMPO抗脂质过氧化作用。结果:OTMPO(4-氧-2,2,6,6-四甲基哌啶氮氧自由基)、HTMPO(4-羟-2,2,6,6-四甲基哌啶氮氧自由基)、HTMPOH(4-羟-2,2,6,6-四甲基羟哌啶)、OTMPOH(4-氧-2,2,6,6-四甲基羟哌啶)有较强的剂量依赖性抑制MDA产生的作用,且OTMPOH,HTMPOH较OTMPO,HTMPO作用强,而OTMP(4-氧-2,2,6,6-四甲基哌啶)、HTMP(4-羟-2,2,6,6-四甲基哌啶)无效。结论:4-TEMPO有较明显的对抗脂质过氧化作用,作为一种临床抗自由基引起的脂质过氧化损伤的药物研究及开发利用,可能有广泛的前景。

The anti-peroxidation of 4-oxy-and 4-hydroxy-nitroxides and its derivatives

OBJECTIVE:The anti-peroxidation of 4-TEMPO (4-oxy-and 4-hydroxy-nitroxides-and-its derivatives) were studied.METHODS:The anti-peroxidation effect of 4-TEMPO in membranes form rat liver,heart and mitochondria were compared by the determination of malondialdehyde (MDA) using TBA colorimetry.RESULTS:OTMPO,HTMPO,OTMPOH and HTMPOH inhibited MDA generation with IC50 6.27～22.32μmol.L-1 in different tissues.The effects of OTMPOH and HTMPOH were stronger than OTMPO and HTMPO.OTMP and HTMP had no effect.CONCLUSION:The results showed that 4-TEMPO were effective,The dosage and efficacy were obviously correlated.Therefore it may be necessary to study it further.