School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, Jinan 250062, China; Shandong Academy Occupational Health and Occupational Medicine, 18877 Jingshi Road, Jinan 250062, China.
Jining Center for Disease Control and Prevention, 26 Yingcui Road, Jining 272000, China.
Toxicology. 2018 Dec 1;410:193-198. doi: 10.1016/j.tox.2018.08.006. Epub 2018 Aug 15.
We explored methods to establish an animal model of manganese poisoning and evaluate the feasibility of the determination method.
Twenty-four specific pathogen-free male rats were randomly divided into four groups: control, low-dose (15.0 mg/kg), middle-dose (25.0 mg/kg), and high-dose (50.0 mg/kg). Intraperitoneal injection of MnCl·HO was administered every 48 h for three months. Rats were tested for behavior, muscle tension, and with a balance beam experiment at the end of each month. Three months later, the rats were sacrificed and brain tyrosine hydroxylase (TH) expression levels were measured.
Rats in each group exhibited changes in behavior, muscle tone, and balance after exposure to manganese, and the scores of each test for the high-dose and middle-dose groups were statistically different from the low-dose and control groups. Finally, a rat model of manganese poisoning was identified with the TH expression less than 30% of the normal value. We find that the modeling success rate of the middle-dose and high-dose groups were 66.67% and 100%, respectively. In addition, there were negative correlations between the three assessment methods such as behavioral tests and TH expression levels.
Intraperitoneal injection of MnCl·HO (25 mg/kg) can successfully establish a manganese poisoning rat model with low mortality rate. Muscle tension, balance beam, and behavioral tests can be used as preliminary determination methods for modeling.
探索建立锰中毒动物模型的方法并评价检测方法的可行性。
24 只 SPF 级雄性大鼠随机分为 4 组:对照组、低剂量组(15.0mg/kg)、中剂量组(25.0mg/kg)和高剂量组(50.0mg/kg)。每 48h 经腹腔注射 MnCl·4H2O 一次,连续注射 3 个月。于每个月末对大鼠进行行为学、肌张力和平衡木实验测试。3 个月后处死大鼠,检测脑酪氨酸羟化酶(TH)表达水平。
各组大鼠在接触锰后均出现行为、肌张力和平衡改变,且高、中剂量组各测试评分与低、对照组比较均有统计学差异。最终确定 TH 表达量低于正常的 30%的大鼠模型为锰中毒模型。中、高剂量组建模成功率分别为 66.67%和 100%。此外,行为学测试和 TH 表达水平之间存在负相关。
腹腔注射 MnCl·4H2O(25mg/kg)可成功建立死亡率低的锰中毒大鼠模型。肌张力、平衡木和行为学测试可作为建模的初步判定方法。