甲基莲心碱对有机磷酸酯抑制的小鼠脑胆碱酯酶的重活化作用

Reactivation of neferine on mice brain cholinesterase inhibited by organophosphate

目的 研究甲基莲心碱 (Nef)对有机磷酸酯中毒小鼠脑胆碱酯酶 (Ch E)的重活化效应。方法 采用微量二巯基双硝基苯甲酸 (DTNB)法测定敌敌畏 (DDVP)体内、体外抑制小鼠脑 Ch E活力 ,观察 0 .0 0 1～ 0 .0 3mg/LDDVP在体外对小鼠脑 Ch E活力的抑制作用 ,比较 Nef和氯磷定体内、体外给药对 DDVP中毒小鼠脑 Ch E的重活化效应。结果 不同浓度的 DDVP显著地抑制试管内小鼠脑 Ch E活力 ,呈现明确的量效关系 ,IC50 为 0 .0 0 3m g/L。 Nef (2 .4 ,4 .8m g/L )与氯磷定 (5 ,12 .5 mg/L )对 0 .0 2 m g/L DDVP体外抑制的小鼠脑 Ch E重活化效应随着浓度增高而加大。对 sc DDVP(10 mg/kg)的小鼠分别 ip Nef或氯磷定 ,其脑 Ch E活率分别为 (4 1.6± 10 .9) %、(5 6 .5± 12 .4 ) % (Nef 15 ,30 mg/kg)和 (2 4 .1± 17.4 ) %、(2 8.4± 11.9) % (氯磷定 2 5 ,5 0 m g/kg) ,两者相比差异显著 (P<0 .0 1)。结论 Nef比氯磷定有更为显著的重活化 Ch E的作用 ,这与 Nef能进入中枢复活脑中毒酶有关。

Object To study the reactivation of neferine (Nef) and pralidoxime chloride (2-PAM·Cl) on mice brain cholinestrase (ChE) inhibited by organophosphate. Methods Micro-DTNB method was used to determine the ChE activity of mice brain inhibited by DDVP in vitro and in vivo, then the inhibitory effect of DDVP (0.001-0.03 mg/L) on mice brain ChE in vitro was observed. The reactivative effect of Nef and 2-PAM·Cl on brain ChE of poisoned mice with DDVP in vivo and in vitro was compared. Results In vitro, the inhibitory effect of DDVP at different concentrations on mice brain ChE showed a concentration-effect relationship. The IC_(50) was 0.003 mg/L. The reactivative effect of Nef (2.4, 4.8 mg/L) and 2-PAM·Cl (5, 12.5 mg/L) on brain ChE inhibited by DDVP (0.02 mg/L) enhanced with increasing their concentrations. In vivo, after 30 min of treated with DDVP (10 mg/L, sc), the mice were given (ip) with Nef (15, 30 mg/kg) or 2-PAM·Cl (25, 50 mg/kg), respectively. The ChE activity rate in these two treated groups were (41.6±10.9) %, (56.5±12.4) % and (24.1±14.3) %, (28.4±11.9) %, respectively. The difference between poisoned group (sc DDVP) and Nef treated group was significant (P<0.01), whereas that between poisoned group and 2-PAM·Cl treated group was not significant (P>0.05). Conclusion The results suggest that Nef have a more remarkable reactivative effect on inhibited brain ChE in vitro and in vivo than 2-PAM·Cl. This may be contributed to that Nef can penetrate the blood-brain barrier.