Doebler J A, Wall T J, Martin L J, Shih T M, Anthony A
Toxicology. 1984 Dec;33(3-4):311-22. doi: 10.1016/0300-483x(84)90047-7.
Quantitative cytochemical techniques were used to monitor effects of the bis-pyridinium oxime HI-6 with and without atropine sulfate (AS) on soman-induced cerebrocortical (layer V) and striatal neuron RNA and acetyl-cholinesterase (AChE) impairments. In addition, plasma cholinesterase (ChE) activity was measured to determine the extent of peripheral enzyme reactivation. Antidotal pretreatment effected complete (HI-6) or partial (AS) amelioration of neuronal RNA depletion evidenced following 1.5 LD50 (195 micrograms/kg) soman, whereas combined HI-6 + AS treatment only partially restored (cortical) or did not change (striatal) neuron RNA contents. HI-6 produced appreciable plasma ChE reactivation but brain AChE activity was not significantly altered. In rats treated only with antidotes, HI-6 or AS alone significantly reduced neuronal RNA in both brain regions. These data indicate that HI-6 influences the metabolic status of central cholinergic compartments and can completely protect against soman-induced neuronal RNA depletion. However, there are no precise relationships among RNA restitution, AChE reactivation or the protective potency of antidotal treatments. Effects of HI-6 on neuronal RNA may signify central cholinolytic activity in vivo, but indirect effects mediated by peripheral mechanisms can not be excluded at present.
运用定量细胞化学技术监测双吡啶肟HI - 6在有或无硫酸阿托品（AS）的情况下，对梭曼诱导的大脑皮质（V层）和纹状体神经元RNA及乙酰胆碱酯酶（AChE）损伤的影响。此外，测量血浆胆碱酯酶（ChE）活性以确定外周酶重新激活的程度。解毒预处理可使1.5倍半数致死量（195微克/千克）梭曼中毒后出现的神经元RNA耗竭得到完全（HI - 6）或部分（AS）改善，而HI - 6 + AS联合治疗仅部分恢复（皮质）或未改变（纹状体）神经元RNA含量。HI - 6可使血浆ChE显著重新激活，但脑AChE活性无明显改变。在仅用解毒剂治疗的大鼠中，单独使用HI - 6或AS均可显著降低两个脑区的神经元RNA。这些数据表明，HI - 6影响中枢胆碱能区室的代谢状态，并可完全防止梭曼诱导的神经元RNA耗竭。然而，RNA恢复、AChE重新激活或解毒治疗的保护效力之间没有精确的关系。HI - 6对神经元RNA的影响可能表明其在体内具有中枢胆碱溶解活性，但目前不能排除由外周机制介导的间接影响。
