丙烯腈对大鼠脑单胺类神经递质及其代谢产物的影响

目的　评价长期低浓度接触丙烯腈对大鼠脑单胺类神经递质及其代谢产物的影响。方法　雄性SD大鼠 30只,随机分成对照组、低剂量组和高剂量组,每组 10只。通过饮水对大鼠进行丙烯腈染毒,分别给予 0、50和 200mg/L的丙烯腈溶液。染毒时间为 12周。染毒结束后从每组随机选取 7只大鼠迅速分离双侧纹状体和小脑皮层,测定单胺类神经递质及其代谢产物的浓度,并取大脑皮层测定单胺氧化酶活性。结果　随着染毒剂量的增加,低剂量组和高剂量组大鼠纹状体中的多巴胺含量分别降低到 (2 .2±0 .7)和 (3 .2±2 .0)μg/g脑湿重,与对照组的多巴胺含量 ( 9. 0±4.2)μg/g脑湿重比较,差异有统计学意义。3组大鼠小脑中的多巴胺未见减少,其代谢产物 3, 4 双羟苯乙酸分别为(186±41)、(245±90)和(115±65)ng/g脑湿重,低剂量组显著升高。3组染毒大鼠纹状体内的 5 羟色胺含量分别为 (249±34)、(155±95)和 (128±101)ng/g脑湿重,呈逐渐下降趋势,并具有显著的剂量 效应关系,但 3组大鼠小脑中的 5- 羟色胺及其代谢产物含量的变化无统计学意义。3组大鼠脑组织纹状体和小脑中的去甲肾上腺素及其代谢产物以及脑皮层单胺氧化酶活性的改变均无统计学意义。结论　丙烯腈对单胺类神经递质及其代谢产物的影响可能是其神经行为毒性的生物学

Effects of acrylonitrile in drinking water on monoamine neurotransmitters and its metabolites in male rat brains

OBJECTIVES: To elucidate the possible involvement of monoamine neurotransmitters in the development of neurobehavioral damage produced by acrylonitrile in drinking water in male rat brains. METHODS: Totally 30 male SD rats were randomly divided into three groups, the control group (n = 10), low dosage group (n = 10), and high dosage group (n = 10), which were respectively administered 0 mg/L, 50 mg/L, 200 mg/L acrylonitrile (AN) in drinking water. The treatment was lasted for 12 weeks. Seven animals were randomly selected from each group for determination of monoamine neurotransmitters in striatum and cerebellum by high performance liquid chromatography with electrochemical detector and activities of monoamine oxidase in cortex. RESULTS: The contents of dopamine in the striatum of low and high dosage groups were decreased to (2.2 +/- 0.7) and (3.2 +/- 2.0) microg/g wet tissue, respectively, and compared with that of control group (9.0 +/- 4.2) microg/g wet tissue, the differences were statistically significant. There were no statistical differences among the contents of dopamine in the cerebellum of all rats, and the levels of 3,4-dihydroxyphenylacetic acid (DOPAC), the major metabolite of dopamine in the cerebellum were (186 +/- 41), (245 +/- 90) and (115 +/- 65) ng/g wet tissue in the control, low and high dosage groups, respectively and in low-dosage group they were significantly higher than those in other groups. There was dosage-dependently decreasing of the contents of serotonin of striatum in the control (249 +/- 34) ng/g wet tissue, low dosage (155 +/- 95) ng/g wet tissue and high dosage groups (128 +/- 101) ng/g wet tissue. CONCLUSION: This study underlines the importance of alterations in the monoamine neurotransmitters system as a possible causative mechanism behind the behavioural and functional changes produced by acrylonitrile.