缺氧环境下4-DMAP形成高铁血红蛋白的药效学特征

Pharmacodynamics of ferrihemoglobin formation by 4-DMAP under hypoxic condition

目的研究高原缺氧环境下4-二甲基氨基苯酚（4-DMAP）形成高铁血红蛋白的药效学特征，为急进高原的氰化物中毒患者救治提供理论参考。方法急性缺氧家兔肌内注射4-DMAP，采集心血，通过比色方法测定高铁血红蛋白。结果急性缺氧对血红蛋白浓度和高铁血红蛋白本底无明显影响，但缺氧升高4-DMAP生成高铁血红蛋白的敏感性，缺氧环境下生成30％～40％高铁血红蛋白（最适抗氰浓度）所需4-DMAP的剂量为20mg／kg，相当于常氧环境所需剂量的68％～80％，当采用常氧环境的最适抗氰剂量（25～30mg／kg）时，缺氧家兔表现严重的缺氧病变，甚至死亡，而且在缺氧家兔体内，高铁血红蛋白维持时间明显延长；4-DMAP的效应还与动物缺氧时间密切相关，高铁血红蛋白生成浓度在1～5天内随缺氧时间增加而升高，5天达到高峰，7天开始回落，但仍然显著高于常氧对照组。结论缺氧提高4-DMAP生成高铁血红蛋白的能力，在缺氧动物体内，高铁血红蛋白代谢慢、维持时间长。

Objective To guide the therapy for cyanide poisoning patients on plateau, the effect of hypoxia on the efficiency of 4-（N, N-dimethyl）-aminophenol （4-DMAP） in ferrihemoglobin （MHb） formation was investigated. Methods Rabbits were raised in hypoxic condition （4500m altitude） as acute-hypoxic animal model, and MHb concentration was determined by spectrophotography at the length of 635nm after 4-DMAP injection. Results There was no difference in hemoglobin content and MHb concentration between acute acutehypoxia group and controls. But in hypoxic rabbits, MHb formation as induced by 4-DMAP was improved distinctly. 30%-40% MHb concentration formation （optimal anti-cyanide concentration） was induced by 20mg/kg 4-DMAP in hypoxic rabbits, compared to 25-30mg/kg in control rabbits. However, when hypoxic rabbits received 25-30mg/kg 4-DMAP, which was the optimal dose for treatment of cyanide poisoning in normoxic animals, the animals manifested even worse symptoms of hypoxia, eren death occurred. Moreover, the level of MHb in acute-hypoxic models maintained longer than that in controls. The effect of 4-DMAP in MHb formation was closely related with duration of hypoxia. During hypoxia period from 1d to 5d, MHb concentration was increased gradually along with the duration of hypoxia, peaking on the 5d, and it started to decline on 7d, but it was still higher than that in control group. Conclusion Hypoxia enhances the effect of 4-DMAP in MHb formation and lowers the metabolism of MHb.