论文部分内容阅读
目的:研究不同剂量氯吡格雷对斑马鱼体大脑核心钟基因bmal,clock,cry和per表达及其生物节律的影响。方法:采用不同浓度氯吡格雷处理斑马鱼1 h后,收集并观察脑组织中生物钟基因bmal、clock、cry、per的mRNA转录水平,并观察氯吡格雷对斑马鱼生物节律,如活动振幅、时相、行为周期和体内褪黑素水平的影响。结果:通过对氯吡格雷处理后斑马鱼大脑中生物钟基因bmal、clock、cry、per的转录水平进行分析发现,氯吡格雷可以显著下调bmal1a、bmal2、clock1a、cry1aa、per1a及per2的表达(P<0.05),同时clock2、cry1bb、per1b及per3的转录水平与氯吡格雷成正相关,发挥应激性补偿作用。经过氯吡格雷处理,斑马鱼的活动振幅和时相显著下调(P<0.05),同时体内褪黑素水平极显著降低(P<0.001)。结论:氯吡格雷摄入导致斑马鱼大脑中主要生物钟基因表达紊乱,影响正常的生物节律及调节睡眠关键激素-褪黑素的分泌水平。
OBJECTIVE: To study the effects of different doses of clopidogrel on the expression of bmal, clock, cry and perinuclear clock genes and their biological rhythms in zebrafish brain. Methods: The zebrafish were treated with different concentrations of clopidogrel for 1 h. The mRNA transcription levels of bclk, clock, cry and per in the brain tissue were collected and observed. The effects of clopidogrel on zebrafish biorhythm, such as amplitude of activity, The phase, the cycle of action and the level of melatonin in the body. Results: The cloning of bmal, clock, cry and per in the brain of zebrafish after clopidogrel treatment showed that clopidogrel significantly down-regulated the expressions of bmal1a, bmal2, clock1a, cry1aa, per1a and per2 <0.05). At the same time, the transcriptional levels of clock2, cry1bb, per1b and per3 were positively correlated with clopidogrel, which played stress compensatory roles. After clopidogrel treatment, the amplitude and phase of zebrafish activity were significantly down-regulated (P <0.05), while the level of melatonin was significantly reduced (P <0.001). CONCLUSION: Clopidogrel intake induces disorder of the major circadian genes in the brain of zebrafish, affecting normal circadian rhythms and regulating the secretion of melatonin, a key sleep hormone.