双复磷对沙林染毒所致兔眼缩瞳及视觉障碍的对抗作用

摘要

目的：评价双复磷对沙林染毒兔眼中毒治疗效果，探讨其作用机制。方法①兔每眼滴注0．1 mL沙林（2μg），染毒后30 min，分别滴眼给予0．1 mL 2．5％，5．0％，7．5％双复磷和1．0％阿托品，观察瞳孔直径及对光反射调节力；②另取36只兔，染毒后30 min，分别滴眼给予上述药物。给药后4 h，测定瞳孔对光反射调节力，眼角膜、虹膜及视网膜乙酰胆碱酯酶（AChE）活性。结果①沙林染毒后，兔眼瞳孔直径及对光反射调节力迅速降低，至染毒后48 h 恢复至正常水平；给予阿托品后，立即出现明显扩瞳，瞳孔直径远高于染毒前水平，但对光反射调节力未见明显恢复，直至给药后48 h，兔瞳孔直径及对光反射调节力恢复正常，恢复时间与染毒组基本相当；给予双复磷，瞳孔直径及对光反射调节力均出现明显升高，并于给药后24 h 恢复正常，恢复时间明显远快于中毒对照组（P ＜0．01），不同浓度双复磷对眼中毒恢复时间的改变无显著差异。②各染毒组兔给药后4 h，与正常对照组动物相比，各给药组对抗反射和调节力眼角膜、虹膜AChE 活性均明显降低（P＜0．01），但视网膜 AChE 活性未见显著改变；与中毒对照组动物相比，给予双复磷对光反射调节力和眼角膜、虹膜 AChE 活性明显升高（P ＜0．01），2．5％，5％和7．5％双复磷组角膜AChE 活性分别为正常对照组的（74±11）％，（80±10）％和（74±7）％，虹膜 AChE 活性分别为（39±9）％，（43±8）％和（43±8）％。给予阿托品对眼角膜、虹膜 AChE 活性无显著改善。结论双复磷对沙林所致眼中毒治疗作用明显优于传统治疗药物阿托品，其作用机制可能与其对活性降低的眼角膜、虹膜AChE 快速重活化作用密切相关。%OBJECTIVE The antagonism of obidoxi me on sarin induced miosis and visual impair-ment was evaluated and its antagonistic mechanism was investigated.METHODS ① 30 min after sarin (2 μg /0.1 mL per eye)was given as an eyedrop,the ability of the 2.5%,5.0%,7.5% obidoxi me and 1 .0% atropine to reverse effects of sarin on pupil dia meter and light reflex were evaluated at different ti mes.② Another 36 rabbits received sarin and at 30 min afer sarin exposure,the drugs above were ad-ministrated and their effects on pupillary light reflex,as well as the AChE activity of cornea,iris and reti-na were recorded 4h after the treatment.RESULTS ① Miosis and impaired pupillary light reflex oc-curred soon after sarin exposure but the abnormal pupil width and pupillary light reflex had disappeared by 48 h after sarin exposure;Subcequent to 1 .0% atropine treatment,the pupil dilatedinstead while the impaired light reflex did not i mprove significantly;unlike atropine,soon after ad ministration of 2.5%, 5.0%,7.5% obidoxi me,the pupil dia meter and light reflex were significantly increased(P <0.01 )and then had beco me normal totally by 24 h post-dose,much faster than those of the control and atropine treatment group.However,there was no significant difference in the recovery ti me between the different dose groups of obidoxi me.② 4h after treatment,the AChE activity in cornea and irisof sarin-treated group were (42 ±4)%,(26 ±2)%,respectively;the AChE activity in cornea of 2.5%,5.0%,7.5%obidoxi me were (74 ±1 1 )%,(81 ±10)% and (74 ±7)%,respectively,and the AChE activity in iris were(39 ±10)%,(43 ±8)% and (43 ±8)%,respectively ,co mpared with sarin-treated group,AChE activities of cornea and iris as well as light reflex of the obidoxi me-treated group were significantly increased(P<0.01 ).But there was no difference in light reflex and AChE activity between the sarin-treated and atropine-treated groups.CONCLUSION Obidoxi me showed better antagonism of sarin-induced ocular effects than that of the commonly used drug,atropine;the antagonistic mechanism is likely closely related to its rapid reactivation of the inhibited AChE in the cornea and iris.