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1,3-二硝基苯诱导的大鼠脑病

1,3-Dinitrobenzene-induced encephalopathy in rats.

作者信息

Philbert M A, Nolan C C, Cremer J E, Tucker D, Brown A W

机构信息

Toxicology Unit, Medical Research Council Laboratories, Carshalton, Surrey, UK.

出版信息

Neuropathol Appl Neurobiol. 1987 Sep-Oct;13(5):371-89. doi: 10.1111/j.1365-2990.1987.tb00192.x.

DOI:10.1111/j.1365-2990.1987.tb00192.x
PMID:3683748
Abstract

Exposure to 1,3-dinitrobenzene (1,3-DNB) in humans induces methaemoglobinaemia, nausea and nervous symptoms. When given to conventional rats, twice-daily oral doses of 10 mg kg-1 1,3-DNB produce methaemoglobinaemia and frequently ataxia after four or five doses. In germ free rats given only a single oral dose of 20 mg kg-1, similar symptoms occur but are of more rapid onset. Light and electron microscope examinations reveal an acute thiamine deficiency-like lesion in the brain stems of both ataxic and apparently normal rats. Bilaterally symmetrical vacuolated lesions involve cerebellar roof, vestibular and superior olivary nuclei and the inferior colliculi. Frequent petechial haemorrhages are associated with these lesions, the erythrocytes usually being limited to enlarged Virchow-Robin spaces but sometimes spreading more widely. The primary cellular targets appear to be astrocytes, oligodendrocytes and vascular elements with secondary neuronal involvement. It is suggested that 1,3-DNB interferes with intracellular redox mechanisms resulting in impaired glucose oxidation.

摘要

人类接触1,3 - 二硝基苯(1,3 - DNB)会引发高铁血红蛋白血症、恶心和神经症状。给常规大鼠每日口服两次剂量为10毫克/千克的1,3 - DNB,四到五次给药后会产生高铁血红蛋白血症,且经常出现共济失调。在仅单次口服剂量为20毫克/千克的无菌大鼠中,会出现类似症状,但发病更快。光学显微镜和电子显微镜检查显示,共济失调和看似正常的大鼠脑干中均出现急性硫胺素缺乏样病变。双侧对称的空泡状病变累及小脑顶、前庭和上橄榄核以及下丘。这些病变常伴有瘀点性出血,红细胞通常局限于扩大的Virchow - Robin间隙,但有时会扩散得更广泛。主要的细胞靶点似乎是星形胶质细胞、少突胶质细胞和血管成分,继发神经元受累。有人认为,1,3 - DNB干扰细胞内氧化还原机制,导致葡萄糖氧化受损。

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