甲胺磷与乙酰甲胺磷对乙酰胆碱酯酶毒效应的比较

目的　探讨高毒有机磷化合物甲胺磷及其替代品乙酰甲胺磷对乙酰胆碱酯酶 (AChE)的抑制作用及机制。方法　提取人红细胞膜及大鼠脑突触体膜后 ,体外实验中用Ellman法测定在不同受试物浓度、不同作用时间下剩余AChE活力 ;整体实验中用Ellman法测定不同脑区AChE活力。结果　乙酰甲胺磷和甲胺磷在体外对人红细胞膜及大鼠大脑皮层突触体膜AChE均有不可逆的抑制作用 ,且有明显的剂量 -效应和时间 -效应关系 ,两者对人红细胞膜及大鼠各脑区突触体膜AChE活力的半数抑制浓度 (IC50 )分别约为 1 0 - 4mol/L、1 0 - 5mol/L ,双分子速率常数 (Ki)分别为 1 0 2mol·L 1 ·min 1 、1 0 3mol·L 1 ·min 1 左右。在整体实验中 ,连续 5d给大鼠腹腔注射乙酰甲胺磷和甲胺磷 ,其全血AChE活力的抑制率逐渐上升 ,第 5天分别达到 68.2 4 %和 54 .80 %。乙酰甲胺磷仅对大鼠脑干AChE活力有抑制作用 (抑制率为 31 .68% ) ,其余脑区均未见明显影响 ;而甲胺磷对各脑区AChE活力均有较强的抑制 ,以小脑和脑干最强 ,分别为 71 .51 %和 61 .85 %。结论　乙酰甲胺磷和甲胺磷在体外对人红细胞膜和大鼠大脑皮层突触体膜AChE活力均有不同程度的抑制作用 ;在整体实验中对大鼠全血AChE活力均有抑制作用。对脑区AChE的抑制存在差异可能是两者毒

Comparison of the toxic effect of methamidophos and acephate on acetylcholinesterase

OBJECTIVE: To explore the inhibitory effects of highly toxic organophosphorus compound and its substitute (methamidophos and acephate) on acetylcholinesterase (AChE) and their toxic mechanisms. METHODS: Ellman method was used to measure AChE activity in vitro and vivo. RESULTS: Acephate and methamidophos could directly inhibit AChE activities in human erythrocyte membrane and rat brain synatosomal membrane in dose- and time-dependent manners in vitro, and this effect was irreversible. The IC50 of acephate and methamidophos affecting human erythrocyte membrane and rat synatosomal membrane were approximately 10(-4) mol/L and 10(-5) mol/L respectively and the Ki were 10(2) mol.L-1.min-1 and 10(3) mol.L-1.min-1 respectively. In vivo, after rats being administered with them for 5 d, the inhibitory rate of AChE activities in blood were increased to 68.24% and 54.80% respectively. When rats being administrated with acephate, there was 31.68% of inhibition on the brain stem, but no significant inhibition in other brain region was noticed, while methamidophos had a strong inhibitory effect on the activity of AChE in all brain regions, especially the cerebellum and brain-stem(71.51% and 61.85% respectively). CONCLUSION: Acephate and methamidophos could directly inhibit the AChE activities in vitro, but the inhibition degree was different. In vivo, both could also inhibit AChE activities in blood. The difference in inhibition on brain regions may be one of the reason of various toxic effect of them.