摘要
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 expression of key clock genes including bmal,clock,cry and per,and the effects of clopidogrel on the biological rhythm.METHODS Zebrafish were treated with different concentrations of clopidogrel for 1 h,to collect and examine the brain tissue mRNA levels of clock genes such as bmal,clock,cry and per,and to monitor the effects of clopidogrel on zebrafish biological rhythm and behaviors（amplitude,phase,period and melatonin levels）.RESULTS With the increase of clopidogrel concentrations,the expressions of bmal1 a,bmal2,clock1 a,cry1aa,per1 a and per2 were significantly decreased（P0.05）,but clock2,cry1 bb,per1b and per3 were significantly increased（P0.05）.Locomoter test showed that zebrafish had significantly decreased amplitude and phase of activities due to the clopidogrel treatment（P0.05）.ELISA analysis suggested that clopidogrel decreased zebrafish melatonin content sharply（P0.001）.CONCLUSION Clopidogrel leads to the disordered expression of circadian clock genes in the zebrafish brain,and also affects the normal zebrafish biological rhythms and melatonin secretion,revealing that clopidogrel treatment may lead to similar symptoms in human.
出处
《中国医院药学杂志》
CAS
北大核心
2017年第14期1370-1373,1378,共5页
Chinese Journal of Hospital Pharmacy
基金
齐齐哈尔市科学计划项目(编号:SFZD2014041)
关键词
氯吡格雷
斑马鱼
生物钟
生物节律
clopidogrel
zebrafish
clock genes
biological rhythm
