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目的:研究2-巯基苯并咪唑(MBI)对 SD 大鼠所产生的毒性反应的性质和程度、剂量和毒性效应的关系、无毒反应剂量以及毒性的主要靶器官。方法:采用 SD 大鼠,灌胃给予 MBI,分为溶媒对照组和3个给药组(MBI 2 mg·kg~(-1),MBI 10 mg·kg~(-1),MBI 50 mg·kg~(-1)),连续给药28 d,期间对体重、摄食量进行监测。给药结束次日解剖取材,测定血液学及血清生化学指标,并对大鼠主要脏器进行大体观察和组织病理学检查。结果:50 mg·kg~(-1)MBI 使大鼠的体重增长及摄食量的增加受到明显抑制;10 mg·kg~(-1)和*或50 mg·kg~(-1)MBI 导致雌雄大鼠甲状腺、脑、肝脏重量明显升高,胸腺、脾脏重量显著下降;使雄性大鼠垂体、肺、睾丸重量明显升高,雌性肾上腺、颚下腺重量显著下降,肾脏重量显著升高;50 mg·kg~(-1)剂量引起大鼠 AST、LDH、CRE、BUN、CHO 等血清生化水平的显著变化;组织病理学检查发现,10 mg·kg~(-1)以上剂量的 MBI 可引起雄性和雌性动物甲状腺增生性病变、垂体前叶β细胞肿胀以及雄性动物胸腺萎缩;50 mg·kg~(-1)MBI 可引起雄性和雌性动物肝损伤,肾上腺皮质细胞的脂肪变性,以及雌性动物肾盂扩张。结论:MBI 毒性作用的主要靶器官为甲状腺;MBI 在 SD 大鼠的最大无毒反应剂量为2 mg·kg~(-1)。
OBJECTIVE: To study the nature and degree of toxicity of 2-mercaptobenzimidazole (MBI) to SD rats, the relationship between dose and toxicity, non-toxic dose and toxic target organ. Methods: The SD rats were given intragastric administration of MBI and were divided into vehicle control group and three administration groups (MBI 2 mg · kg -1, MBI 10 mg · kg -1, MBI 50 mg · kg -1) kg ~ (-1)) for 28 days. The body weight and food intake were monitored during the period. The day after the administration was finished, the hematology and serum biochemistry indexes were determined, and the main organs of rats were observed and histopathologically examined. Results: MBI at 50 mg · kg -1 significantly inhibited body weight gain and food intake, while MBI at 10 mg · kg -1 and 50 mg · kg -1 resulted in The weight of thyroid, brain and liver in male and female rats increased significantly, the weight of thymus and spleen decreased significantly, the weight of pituitary, lung and testis in male rats increased significantly, the weight of female adrenal gland and mandibular gland decreased significantly, and the weight of kidney increased significantly. Serum biochemical levels of AST, LDH, CRE, BUN and CHO were significantly changed in the dose of 50 mg · kg -1. Histopathological examination showed that the MBI of above 10 mg · kg -1 Causing male and female thyroid hyperplasia lesions, anterior pituitary β cell swelling and thymus atrophy in male animals; 50 mg · kg -1 MBI induced liver injury in males and females, steatosis of adrenocortical cells, Animal pelvis dilated. CONCLUSION: The main target organ of MBI toxicity is thyroid. The maximum non-toxic dose of MBI in SD rats is 2 mg · kg -1.