兰州大学机构库 >生命科学学院
2,4-二氯苯酚致草鱼原代肝脏细胞凋亡及其作用机理研究
Alternative TitleMechanism research on apoptosis induced by 2,4-DCP in primary hepatocytes of grass carp (Ctenopharyngodon idella)
李慧
Thesis Advisor张迎梅 ; 黄德军
2013-11-30
Degree Grantor兰州大学
Place of Conferral兰州
Degree Name博士
Keyword2,4-二氯苯酚(2,4-DCP) 草鱼 原代肝细胞 细胞凋亡 B细胞淋巴瘤/白血病-2(Bcl-2) Bcl-2相关X蛋白(Bax) 活性氧(ROS) 肿瘤坏死因子(TNF-α) 凋亡抑制蛋白(IAP)
Abstract氯酚类化合物是一类主要的环境污染物,常被用作杀菌剂、农药和除草剂等,其在环境中特别是水体中能稳定存在。2,4-DCP作为氯酚类化合物的一种,主要用于除草醚、2,4-滴的合成,由于其大量用于工农业并被释放到环境中,不仅影响生物体的生长、发育和生殖,还可以在细胞和分子水平导致氧化应激、促使自由基的产生,影响相关基因的表达,甚至引起细胞死亡。 细胞凋亡是指程序性的细胞死亡,可由线粒体信号或死亡受体等介导发生。已有研究证明2,4-DCP可以诱导细胞凋亡,但其诱导细胞凋亡的信号途径和分子机制尚不清楚。本实验以草鱼的原代肝细胞为材料,通过测定2,4-DCP染毒后细胞的活力、细胞凋亡和线粒体膜电位,检测细胞内活性氧的含量及凋亡相关因子的mRNA表达情况,探讨了2,4-DCP诱导细胞凋亡的信号途径;通过加入线粒体保护剂ALC进一步验证了线粒体信号途径在2,4-DCP诱导细胞凋亡过程中的作用,最终揭示了2,4-DCP诱导细胞凋亡的具体途径及分子机制,为2,4-DCP毒性作用机理的研究提供一定的科学依据。本论文具体研究结果如下: 1. 2,4-DCP暴露可以抑制草鱼原代肝细胞的细胞活力。 2. 2,4-DCP暴露可以诱导草鱼肝细胞的凋亡。 3. 2,4-DCP暴露可以引起草鱼肝细胞线粒体膜电位的降低。 4. 2,4-DCP暴露可以导致草鱼肝细胞的ROS的产生。 5. 2,4-DCP暴露可以诱导草鱼肝细胞凋亡相关基因的改变。 6. ALC(5 mM)抑制了2,4-DCP导致的草鱼肝细胞的凋亡,并显著恢复了线粒体膜电位,降低了caspase-3、TNF-α和Bax mRNA的表达量以及Bax/Bcl-2 mRNA的比值。 7. 2,4-DCP暴露引起草鱼肝细胞IAP mRNA表达量的下降,但对草鱼IAP蛋白的表达没有影响。 以上结果表明:2,4-DCP诱导的草鱼肝细胞的凋亡是通过线粒体信号途径介导的。2,4-DCP染毒细胞后通过产生ROS引起氧化应激,降低线粒体膜电位,改变caspase-3和Bax mRNA的表达以及Bax/Bcl-2比值,最终导致细胞凋亡。
Other Abstract2,4-DCP can affect the growth, development, induce oxidative stress, change the expression of related genes and even lead to apoptosis. 2,4-DCP has been demonstrated to induce apoptosis, but the detailed mechanism remains unclear. Therefore, in this study the changes in grass carp hepatocytes exposed to 2,4-DCP were detected. Mitochondrial protective agent ALC was added to further explore the relationship of 2,4-DCP-induced apoptosis and mitochondrial pathway. The results were as follows: 1. 2,4-DCP inhibited the cell viability of grass carp primary hepatocytes. 2. 2,4-DCP induced apoptosis in grass carp hepatocytes. 3. 2,4-DCP decreased the Δψm of grass carp hepatocytes. 4. 2,4-DCP caused ROS production in grass carp hepatocytes. 5. 2,4-DCP changed the mRNA expression of apoptosis related genes in grass carp hepatocytes. 6. ALC inhibited the 2,4-DCP-induced apoptosis and significantly restored the Δψm, reduced caspase-3, TNF-α and Bax mRNA expression and the ratio of Bax/Bcl-2 mRNA. In conclusion, the results reveals the 2,4-DCP-induced apoptosis pathway and its molecular mechanism, provides scientific research basis for the research of 2,4-DCP.
URL查看原文
Language中文
Document Type学位论文
Identifierhttps://ir.lzu.edu.cn/handle/262010/222096
Collection生命科学学院
Recommended Citation
GB/T 7714
李慧. 2,4-二氯苯酚致草鱼原代肝脏细胞凋亡及其作用机理研究[D]. 兰州. 兰州大学,2013.
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