四-(对氨基苯基)钴卟啉-NO配合物的合成及NO释放效能和生物学活性

Synthesis, NO Releasing Efficiency and Bioactivities of Complex Nitrosyl meso-Tetrakis(4-aminophenyl)porphyrin Cobalt

合成并结构表征meso-5,10,15,20-四(对氨基苯基)钴卟啉-NO配合物(TAPP-Co-NO)作为NO供体.采用重氮化和偶合反应检测TAPP-Co-NO体外NO的释放效果.选取家兔离体胸主动脉环测TAPP-Co-NO对家兔离体胸主动脉环舒张作用.大鼠随机分为两组,实验组静脉给予0.5mL二甲基亚砜和TAPP-Co-NO混合液,对照组静脉给予等量二甲基亚砜,观察两组大鼠收缩压、舒张压和心率的变化.TAPP-Co-NO的释放效率为63.17%.TAPP-Co-NO能使甲氧胺引起家兔离体胸主动脉收缩的量效关系曲线非平行地右移,最大反应(Emax)压低(P<0.01),压低百分率为55.7%.实验组大鼠血压在用药后第5s时开始下降,第10s时下降幅度达最大,以后逐渐回升,第60s时接近用药前水平;对照组大鼠,血压水平在用药前后没有统计学差异;实验组和对照组大鼠的心率在用药前后均无统计学差异.结果表明,TAPP-Co-NO有较高的释放效率,能明显抑制甲氧胺对家兔离体胸主动脉的收缩,具有瞬间降压作用.

To synthesize nitrosyl meso-tetrakis（4-aminophenyl）porphyrin cobalt （TAPP-Co-NO） as NO donor, the NO-releasing property of TAPP-Co-NO in aqueous solution was studied by diazotization at room temperature. Next, the relaxation of TAPP-Co-NO was investigated on isolated aorta pectoralis circle in the rabbit. Finally, eighteen rats were randomized into two groups. The treatment group was injected venously with 0.5 mL of TAPP-Co-NO mixed DMSO, and the control group was given with 0.5 mL of DMSO. The systolic blood pressure （SBP）, diastolic blood pressure （DBP） and heart rates （HR） were measured before and after administration. NO-releasing ratio of TAPP-Co-NO was 63.17%. TAPP-Co-NO shifted methoxamine cumulative dose-response curves rightward im-paralleled and reduced the maximal response （Emax）, the reduced percentage was 55.7%. For the treatment group, the blood pressure of rats began to decrease at the time of 5 s after the administration. The blood pressure of rats reached minimum at the time of 10 s, then increased gradually, and finally, approached normal blood pressure at 60 s. For the control group, the blood pressure of the rats was not changed after employing the DMSO. The results show that NO-releasing ratio of the TAPP-Co-NO was relatively high and it could decrease blood pressure instantaneously.