1,2-二氯乙烷对SD大鼠亚急性吸入毒性研究

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目的确定1,2-二氯乙烷(1,2-DCE)亚急性吸入的毒性作用和靶器官。方法无特定病原体级健康成年SD大鼠64只,雌雄各半,随机分为对照组、低剂量组和高剂量组。采用口鼻式动式吸入染毒法,低和高剂量组予质量浓度为600和1 800 mg/m3的1,2-DCE染毒8 h/d,连续7 d;对照组吸入新鲜空气。染毒期间称量大鼠体质量,观察其活动状况。实验结束后,检测大鼠血常规和血清血生化指标;解剖、分离主要脏器计算脏器系数,并进行组织病理学检查。结果染毒后第4~7天,高剂量组雌性和雄性大鼠体质量均分别低于同性别对照组(P<0.05),并从染毒后第3天开始出现不同程度的体质量负增长(P<0.05)。雌性高剂量组大鼠血清天冬氨酸氨基转移酶、γ-谷氨酰基转移酶、乳酸脱氢酶的活力和甘油三酯、尿素氮、肌酐的水平均高于雌性对照组(P<0.05)。高剂量组大鼠脑、肝脏、肺脏的脏器系数均分别高于对照组(P<0.05);与雌性对照组比较,雌性高剂量组大鼠心脏、肾脏和肾上腺的脏器系数均升高(P<0.05),脾脏脏器系数下降(P<0.05);雄性高剂量组大鼠肾脏和肾上腺的脏器系数均高于雄性对照组(P<0.05)。肉眼可见大鼠脑、肝脏和肾脏大体形态学改变。组织病理学检查结果显示,高剂量组部分大鼠出现大脑皮质和血管周围空泡化,小脑颗粒细胞坏死等脑水肿病变;部分大鼠肝脏可见肝细胞水肿;部分大鼠肾脏可见肾小管蛋白沉积、肾小管上皮细胞水肿、肾小管扩张等病理改变,并可见肾小管上皮细胞异型性。各组大鼠血常规指标未出现有生物学意义的改变;低剂量组大鼠血清血生化指标基本未出现有生物学意义的改变。结论 1,2-DCE亚急性吸入可引起大鼠脑水肿、肝脏和肾脏损害;大脑、小脑、肝脏和肾脏是1,2-DCE亚急性吸入毒性作用的靶器官;1,2-DCE毒作用存在性别差异。 Objective To determine the toxic effects and target organs of subacute inhalation of 1,2-dichloroethane (1,2-DCE). Methods Sixty-four healthy adult SD rats without specific pathogen were randomly divided into control group, low dose group and high dose group. Rats in low and high dose groups were treated with 1,2-DCE at a concentration of 600 and 1800 mg / m3 for 8 h / d for 7 days, respectively. In the control group, fresh air was inhaled. The body weight of rats was weighed during exposure to observe their activity status. After the experiment, blood and serum biochemical indexes of rats were detected. Anatomy and separation of major organs were performed to calculate organ coefficients and histopathological examination. Results The body weight of female and male rats in high dose group were lower than that of the same sex group on the 4th and 7th day after exposure (P <0.05), and negative body mass growth appeared on the 3rd day (P <0.05). Serum aspartate aminotransferase, γ-glutamyl transferase, lactate dehydrogenase activity and triglyceride, urea nitrogen, creatinine levels in female high-dose group were higher than those in female control group (P <0.05 ). The organ coefficients of brain, liver and lung of high dose group were higher than those of control group (P <0.05). Compared with female control group, the organ coefficient of heart, kidney and adrenal of high dose group increased (P <0.05), and the spleen organ coefficient decreased (P <0.05). The indexes of kidney and adrenal in male high-dose group were higher than those in male control group (P <0.05). Macroscopic brain, liver and kidney gross morphological changes. Histopathological examination showed that some rats in the high-dose group showed cerebral edema such as cerebral cortex and perivascular vacuolization, necrosis of cerebellar granulosa cells, and the like; some rat liver showed hepatocyte edema; some rats showed renal tubular protein deposition , Tubular epithelial cell edema, tubular dilatation and other pathological changes, and visible renal tubular epithelial cell atypia. There were no biological changes in the blood indexes of rats in all groups. The serum biochemical indexes of rats in low-dose groups basically did not change in biological significance. Conclusion Subacute inhalation of 1,2-DCE can cause cerebral edema, liver and kidney damage in rats. Cerebral, cerebellum, liver and kidney are the target organs of subacute inhalation toxicity of 1,2-DCE. 1,2-DCE toxicity There are gender differences.
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