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Wistar大鼠急性敌草快中毒模型的建立与评估

Establishment and evaluation of acute diquat poisoning model in Wistar rats

摘要目的 建立敌草快急性中毒Wistar大鼠模型,观察敌草快导致大鼠主要靶器官的病理损害.方法 将36只SPF级Wistar大鼠随机分为46.2、77.0、115.5、231.00、346.5 mg/kg 5个染毒剂量组及生理盐水对照组,每组6只,分别给予一次性灌胃染毒.记录大鼠的一般情况,采用苏木素-伊红(HE)和Masson染色法观察肺、肝、肾组织的病理变化,根据一般情况与病理变化确定最佳染毒剂量.将36只SPF级Wistar大鼠随机分为1、3、7、11、14 d 5个时间组和对照组,每组6只,按选定的最佳剂量给予一次性灌胃染毒,分别在染毒后1、3、7、11、14 d处死.记录大鼠的一般情况,通过化学比色法检测血清中谷丙转氨酶(ALT)和谷草转氨酶(AST)活力,采用HE和Masson染色法观察肺、肝、肾组织的病理变化.结果 与生理盐水对照组比较,各染毒剂量组大鼠均出现不同程度的体重下降.46.2、77.0、115.50 mg/kg染毒剂量组在染毒第14天全部存活,231.0 mg/kg染毒剂量组中2只大鼠分别于染毒第3、5天死亡, 346.5 mg/kg染毒剂量组中3只大鼠分别于染毒第4、5天死亡.依据不同染毒剂量染毒后大鼠14 d的生存率、中毒症状和病理变化确定115.5 mg/kg为最佳染毒剂量.用115.5 mg/kg给予大鼠一次性灌胃染毒,与对照组比较,染毒第1、3天大鼠血清AST、ALT活力较高,差异均有统计学意义(P<0.05).组织病理检查显示:115.5 mg/kg染毒剂量组大鼠肺、肝、肾组织均在染毒第1天开始出现病理反应,第3天病理变化最重,之后逐渐减轻;第14天仍可见大鼠肺泡隔轻度增宽,炎性细胞浸润,局部肺泡腔变窄、萎缩,周围肺泡代偿,支气管及肺泡间隔可见胶原纤维增生,局部肾小管上皮细胞体积增大、坏死;肝中央静脉周围肝细胞空泡样变性,呈点状坏死.结论 一次性灌胃染毒可成功诱导急性敌草快中毒大鼠模型,用115.5 mg/kg染毒剂量造模,可全程观察Wistar大鼠病情变化及主要靶器官的病理损害规律.

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abstractsObjective To establish the Wistar rat model of acute diquat poisoning and observe the pathological damage of main target organs. Methods Thirty-six Wistar rats were randomly divided into six groups(n=6), including one normal saline control group and five treatment groups which were separately given single-dose of intragastric administration at the doses of 46.2 mg/kg, 77.0 mg/kg, 115.5 mg/kg, 231.0 mg/kg and 346.5 mg/kg.The pathological changes of lung, liver and kidney were observed by hematoxylin and eosin (HE) and Masson staining. The optimal dose was determined according to the general situation and pathological changes. Thirty-six Wistar rats were randomly divided into five treatment groups and one normal saline control group. Treatment groups were given single-dose of intragastric administration according to the optimal dose. The rats were sacrificed at 1st, 3rd, 7th, 11th and 14th day after exposed, respectively. The activity of serum glutamic-pyruvic transaminase (ALT) and glutamic-oxalacetic transaminase (AST) were measured by chemical colorimetry. The pathological changes of lung, liver and kidney were observed by HE and Masson staining.Results According to 14 d survival rate, the toxic symptoms and pathological changes, 115.50 mg/kg was determined the best dose. Given single-dose of intragastric administration at the doses of 115.50 mg/kg, it was found that the serum AST and ALT activity of rats on the first and third day of exposure was significant higher than those in control group. The results of pathological examination exhibited that in 115.50 mg/kg group, the pathological changes of lung, liver and kidney began to appear on the first day of exposure, the pathological changes were the most serious on the third day, and then gradually alleviated.On the 14th day, the alveolar septum was slightly widened, with inflammatory cell infiltration, local alveolar cavity became narrow, atrophy, peripheral alveolar compensation, bronchi and alveolar septum collagen fiber proliferation; The local renal tubular epithelial cells were enlarged and necrotic; the central vein surrounding hepatic cells showed vacuolar degeneration with punctate necrosis. Conclusion The rat model of acute diquat poisoning can be successfully induced by single-dose of intragastric administration.The condition of wistar rats and the pathological damage of the main target organs could be observed during the whole course of 115.50 mg/kg administration.

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中华劳动卫生职业病杂志

中华劳动卫生职业病杂志

2019年37卷5期

342-346页

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