锰暴露对雄性大鼠肝功能酶谱影响的时间毒性

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目的研究不同时间点的锰暴露对雄性大鼠肝功酶活性的影响,为锰的毒性评价与防治提供科学依据。方法健康成年雄性SD大鼠96只,在严格控制光照/黑暗(12h:12h)条件下适应性喂养7天后,随机分为4个对照组与4个锰暴露组,分别于一天中的ZT2、ZT8、ZT14与ZT20授时时间点对锰暴露组腹腔注射30mg/kg Mn Cl2,对照组等剂量腹腔注射蒸馏水,每天1次,连续21天。第22天,处死动物,获取动物血清,检测其丙氨酸转氨酶(ALT)、天门冬氨酸转氨酶(AST)、碱性磷酸酶(ALP)及酸性磷酸酶(ACP)活性。分析各指标的组间差异及昼夜节律。结果锰暴露可引起雄性大鼠血清肝功酶活性的改变,且不同的时间点暴露,结果却不相一致。在授时时间点ZT2暴露其酶谱改变较相一致,而其他的授时时间点暴露特别是ZT8其酶谱改变差异较大。余弦分析结果显示ALT、AST、ACP与ALP日均值均下降,ALT与AST振幅减少、ACP与ALP振幅增加,ALT与ACP的峰值时间延迟、而AST与ALP的峰值时间提前。其中ALP对照组具昼夜节律特性(P<0.05),而锰暴露后昼夜节律消失(P>0.05)。结论锰暴露引起的血清肝功酶活性改变具时间差异性,且可导致其生物节律紊乱;在安排锰暴露工人的工作时间时,需尽可能地避开毒性最大的时段。在进行锰肝毒性评价时,需尽可能地安排在毒性反应相一致的时间点进行。 Objective To study the effects of manganese exposure at different time points on hepatic enzyme activity in male rats and provide a scientific basis for the evaluation and prevention of manganese toxicity. Methods Ninety-six healthy adult male Sprague-Dawley rats were randomly divided into four control groups and four manganese exposure groups under the control of light / dark (12h: 12h) for 7 days. ZT2, ZT8, ZT14 and ZT20 at the time point of exposure to manganese exposure group intraperitoneal injection of 30mg / kg MnCl2, the control group of equal dose of intraperitoneal injection of distilled water, once daily for 21 days. On the 22nd day, the animals were sacrificed and the serum of the animals was taken for detecting ALT, AST, ALP and ACP activities. Analysis of the indicators of the differences between groups and circadian rhythm. Results Manganese exposure could cause changes of serum liver enzyme activity in male rats, and the results were not consistent at different time points. ZT2 exposure time at the time point of its zymogram changes more consistent, and other time-point exposure, especially zt8 its zymogram changes vary greatly. Cosine analysis showed that daily mean ALT, AST, ACP and ALP decreased, ALT and AST amplitude decreased, ACP and ALP amplitude increased, ALT and ACP peak time delay, and AST and ALP peak time advanced. The ALP control group had circadian rhythm characteristics (P <0.05), while the circadian rhythms disappeared after exposure to manganese (P> 0.05). Conclusion The change of serum liver enzyme activity caused by manganese exposure has the time difference and can lead to the disorder of its biological rhythm. When arranging the working hours of manganese exposure workers, it is necessary to avoid the period of toxicity as much as possible. In the evaluation of manganese toxicity, should be arranged as much as possible at the point of time when the toxic reaction.
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