成瘾剂量下烟碱对大鼠的毒性损伤

摘要

为研究成瘾剂量下烟碱对大鼠的毒性作用,采用皮下注射方式和条件位置偏好(CPP)装置构建了SD大鼠的烟碱依赖模型,考察了成瘾初期和持续期SD大鼠对烟碱依赖的变化,并对烟碱成瘾大鼠血常规、血生化等生理指标以及各器官的病理学改变进行了研究.结果表明:①采用0.2 mg/kg给药剂量,在第5次给药周期后,大鼠形成了稳定的烟碱依赖,在持续给药的过程中大鼠对烟碱的依赖程度呈现先升高后与成瘾初期持平的趋势.②烟碱能引起大鼠炎症相关指标嗜酸性粒细胞百分率(EOS)表达量下调,以及肝脏损伤相关指标γ-谷氨酰转肽酶(GGT)及总胆红素(TBIL)的上调;③烟碱暴露在一定程度上能引起大鼠的肾脏和肝脏轻度水肿;肺部有较明显病理症状,且以炎症为主.因此,成瘾剂量(0.2 mg/kg)暴露下烟碱会对大鼠产生轻度的毒性,对肺部、肝脏及免疫系统造成一定的毒性损伤.%To study the toxicity of nicotine at addictive dosage using rats as a model, SD rats were injected with nicotine subcutaneously, meanwhile the nicotine-dependence model of rat was established by using CPP apparatus, and the variation of initial nicotine-dependence duration was investigated successively. The blood count parameters, blood biochemistry and histopathology of each organ of nicotine-dependent rat were studied. The results showed that: 1) 0.2 mg/kg nicotine induced stable nicotine-dependence in rats after five dosing periods, and the degree of nicotine dependence increased first and then decreased to the level at the initial stage of addiction. 2) The results of blood count parameters and blood biochemistry indicated that nicotine down-regulated the expression of inflammatory index EOS and up-regulated the levels of liver damage-related GGT and TBIL. 3) Histopathology results indicated that nicotine caused mild edema of liver and kidney in rats, the distinct pathological damage of lung was mainly inflammatory injury. Therefore, nicotine had mild toxicity for rats at nicotine-dependence dosage (0.2 mg/kg), the lung, liver and immune system of rats suffered different degrees of toxic damage due to nicotine.