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乙酰胆碱酯酶抑制剂甲基膦酸频哪酯(梭曼)对禁食和进食大鼠特定内分泌、葡萄糖及儿茶酚胺水平的影响。

Effects of the acetylcholinesterase inhibitor pinacolyl methylphosphonofluoridate (soman) on selected endocrine, glucose, and catecholamine levels in fasted and fed rats.

作者信息

Fletcher H P, Noble S A, Spratto G R

机构信息

Department of Pharmacology and Toxicology, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, IN 47907.

出版信息

Toxicology. 1988 Nov 30;52(3):323-9. doi: 10.1016/0300-483x(88)90136-9.

Abstract

Fed and 18-h fasted rats were given acute doses of either saline or the acetylcholinesterase inhibitor pinacolyl methylphosphonofluoridate (soman) 40, 60, or 80 micrograms/kg. After 30 min plasma samples were collected and assayed for glucose, insulin, glucagon, corticosterone, epinephrine and norepinephrine and the hypothalamus was isolated and assayed for acetylcholinesterase activity. Toxic sign scores were determined and they indicated that soman may be more toxic in the fasted rat. Soman-induced increases in corticosterone were observed in both fasted and fed rats; these levels were significantly higher in fasted rats given either soman or saline. Also, soman-induced increases in glucagon were more pronounced in fasted rats. Soman also caused an apparent dose-dependent increase in catecholamines and a decrease in hypothalamic acetylcholinesterase activity in both groups of rats. The expected lower insulin and glucose levels in the fasted rats were present in the saline-dosed animals and remained lower than fed rats after each dose of soman. This lack of soman-induced hyperglycemia may contribute to the toxicity of soman in fasted rats.

摘要

给喂食的大鼠和禁食18小时的大鼠急性注射生理盐水或乙酰胆碱酯酶抑制剂甲基膦酸频那酯(梭曼),剂量分别为40、60或80微克/千克。30分钟后采集血浆样本,检测葡萄糖、胰岛素、胰高血糖素、皮质酮、肾上腺素和去甲肾上腺素水平,分离下丘脑并检测乙酰胆碱酯酶活性。确定中毒体征评分,结果表明梭曼对禁食大鼠的毒性可能更大。在禁食和喂食的大鼠中均观察到梭曼诱导的皮质酮水平升高;给予梭曼或生理盐水的禁食大鼠中,这些水平显著更高。此外,禁食大鼠中梭曼诱导的胰高血糖素升高更为明显。梭曼还导致两组大鼠儿茶酚胺明显呈剂量依赖性增加,下丘脑乙酰胆碱酯酶活性降低。生理盐水给药的禁食大鼠中出现了预期的较低胰岛素和葡萄糖水平,并且在每次注射梭曼后仍低于喂食大鼠。梭曼诱导的高血糖症的缺乏可能导致梭曼对禁食大鼠的毒性。

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