锰毒性不同病程动物模型的建立与评价

发布时间：2018-11-17 16:50

【摘要】：目的采用氯化锰染毒建立锰毒性不同病程的动物模型并对其进行评价。方法 120只雄性SD大鼠按体重随机分为染锰30 d组、染锰90 d组与染锰90 d后再恢复30 d组及其相应的对照组,染锰组按6 mg(Mn)/kg·BW每日腹腔注射氯化锰溶液,对照组给予生理盐水。各组试验结束后进行体重、脏体比、食物利用率、血液学指标、血清生化指标、血清Mn、Fe、Mg等离子、黑质多巴胺能神经元活性的测定与分析以及肝脏、肾脏与睾丸等的病理组织学观察与分析。结果各染毒组大鼠的体重以及食物利用率与其相应对照组比较,差异均无统计学意义(P0.05);各染毒组血清中Mn含量及Mn/Fe比值与相应对照组比较均升高,差异有统计学意义(P0.05);以HE染色进行病理形态学观察,发现各染毒组与其相应对照组比较均出现不同程度的肝细胞核变性坏死以及睾丸曲细精管部分管腔内精子数减少,初级精母细胞空胞样变性等,且随染锰时间延长有加重的趋势,但脱离锰暴露后(90 d染毒+30 d恢复)病变有恢复迹象;酪氨酸羟化酶免疫组织化学染色观察发现各时间点染毒组与其相应对照组比较,脑组织中TH-阳性的多巴胺能神经元数量均减少,并且随着染锰时间的延长减少程度加重,脱离锰暴露后(90 d染毒+30 d恢复)损伤不可恢复。结论根据以上各指标综合判断,本次研究所建立的锰毒性不同病程的动物模型是成功的,为今后锰毒性机制的进一步研究提供了可靠的动物模型基础。
[Abstract]:Objective to establish animal models of manganese toxicity in different course and evaluate it. Methods 120 male SD rats were randomly divided into two groups according to their body weight: manganese exposure group (90 d), manganese exposure group (30 d) and corresponding control group. Manganese chloride solution was injected intraperitoneally according to 6 mg (Mn) / kg BW daily in manganese exposed group. The control group was given normal saline. Body weight, visceral body ratio, food utilization rate, hematologic index, serum biochemical index, serum Mn,Fe,Mg plasma, dopaminergic neuron activity in substantia nigra and liver were measured and analyzed. Histopathological observation and analysis of kidney and testis. Results there was no significant difference in body weight and food utilization rate between the two groups (P0.05). The content of Mn and the ratio of Mn/Fe in serum of each exposed group were higher than those of the corresponding control group (P0.05). HE staining was used to observe the pathomorphology. It was found that the degenerative necrosis of liver nucleus, the decrease of spermatozoa in some lumen of testicular tubule, and the vacuolar degeneration of primary spermatocyte were found in each group compared with the corresponding control group. With the prolongation of the time of manganese exposure, there was a tendency of aggravation, but the pathological changes showed signs of recovery after exposure to manganese (90 days after exposure to 30 days of recovery). The results of immunohistochemical staining of tyrosine hydroxylase showed that the number of TH- positive dopaminergic neurons in brain tissue decreased in each time group compared with the corresponding control group, and increased with the prolongation of manganese exposure time. The injury could not be recovered after exposure to manganese (90 days after exposure for 30 days). Conclusion according to the above indexes, the animal model of manganese toxicity in different course is successful, which provides a reliable basis for further study on the mechanism of manganese toxicity in the future.
【作者单位】：北京市疾病预防控制中心;北京市预防医学研究中心卫生毒理所北京市食物中毒诊断溯源技术重点实验室;首都医科大学公共卫生与家庭医学学院;北京中研同仁堂医药研发有限公司;
【基金】：国家自然科学基金(81373028) 北京市“十百千”卫生人才培养专项经费资助(“十”层次)(2009) 北京市卫生系统高层次卫生技术人才培养项目资助(2011)
【分类号】：R-332

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