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2-溴-4′-硝基苯乙酮对秀丽隐杆线虫寿命的影响及其机制的研究

作者:润色论文网  来源:www.runselw.com  发布时间:2019/10/26 14:28:17  

摘要:延年益寿是人类古往今来的共同夙愿,而延长寿命与减缓衰老也逐渐成为当今生命科学研究领域的热点课题之一。寿命的调控机制较为复杂,由基因遗传和外界环境两者共同作用,其中基因具有决定性的作用,但其作用机理尚未明确。

2-溴-4'-硝基苯乙酮是一种重要的化合物,广泛用于α-胰凝乳蛋白酶,有机合成材料医药中间体中甲硫氨酸残基的修饰;通过实验发现,2-溴-4'-硝基苯乙酮还可以延长秀丽隐杆线虫的寿命,因此研究它具有重要的意义。本课题以秀丽隐杆线作为模式生物,通过化合物2-溴-4′-硝基苯乙酮对其寿命及表型特征的影响,致力于从基因方面为切入点探究其寿命调控分子机理,最终可以通过控制饮食减缓甚至逆转衰老进程而延长寿命。

论文通过三种不同浓度(1 ?g/ mL,5 ?g/ mL,10 ?g/ mL)的2-溴-4′-硝基苯乙酮来喂养野生型秀丽隐杆线虫以及突变体daf-16,突变体pmk-1和突变体pmk-3,探究它们在不同浓度下(1 ?g/ mL,5 ?g/ mL,10?g/ mL)对秀丽隐杆线虫寿命的影响,通过实验发现,暴露在2-溴-4′-硝基苯乙酮的N2型野生型秀丽隐杆线虫寿命普遍会延长,说明2-溴-4′-硝基苯乙酮具有延长线虫寿命的作用,且秀丽隐杆线虫在浓度1 ?g/ mL的2-溴-4′-硝基苯乙酮溶液中延长寿命的作用最强,这说明秀丽隐杆线虫对食物具有一定的浓度依赖性;而突变体daf-16,突变体pmk-1与突变体pmk-3的寿命缩短,这说明基因daf-16与pmk-1,pmk3可能参与了秀丽隐杆线虫的寿命调控,从而得出结论:秀丽线虫的寿命调控机制是通过胰岛素通道与P38途径来实现的。

此外,通过实验发现,秀丽隐杆线虫的寿命不仅与自身相关,而且与所生存的环境因素有密切的关系,例如如果改变它所生存的温度,或是将秀丽隐杆线虫暴露于重金属离子或是绿脓杆菌条件下,其寿命明显缩短,但是喂食了2-溴-4′-硝基苯乙酮的秀丽隐杆线虫寿命仍然强于对照组,这说明化合物2-溴-4′-硝基苯乙酮在秀丽隐杆线虫体内具有热应激性,抗重金属性以及抗绿脓杆菌性。

本论文通过模式生物秀丽线虫,以化合物(2-溴-4′-硝基苯乙酮)来研究秀丽隐杆线虫寿命调控的分子机制尚属首次,不仅扩宽了研究寿命分子机制的范围,而且为探究人类寿命提供了理论依据。

Longevity is a common aspiration of mankindthroughout the ages, and prolonging life and slowing down aging has graduallybecome one of the hot topics in the field of life science study. The regulationmechanism of lifespan is complicated, and it is affected by both genes andexternal environment, in which genes play a crucial role, but the mechanism ofaction is not clear.

2-bromo-4'-nitroacetophenone is animportant compound widely used in the modification of methionine residues inα-chymotrypsin, organic synthetic materials and pharmaceutical intermediates.Experiments found that 2-bromo-4'-nitroacetophenone can also extend thelifespan of C. elegans, so it is of great significance to study it. In thisstudy, Caenorhabditis elegans (C. elegans) is used as model organism toinvestigate the molecular mechanism of lifespan regulation in terms of genes,through the influence of compound 2-bromo-4'-nitroacetophenone on its lifespanand phenotype, so as to prolong life by slowing down or even reversing theaging process through control of the diet.

In this paper, wild type C. elegans, mutantdaf-16, mutant pmk-1 and mutant pmk-3 were fed with three differentconcentrations (1 μg/mL, 5 μg/mL, 10 μg/mL) of 2-bromo-4'-nitroacetophenone, toexplore the influence on lifespan of C. elegans at different concentrations (1μg/mL, 5 μg/mL, 10 μg/mL).

The study found that the lifespan was generallyextended for wild type N2 C. elegans exposed to 2-bromo-4'-nitroacetophenone,indicating 2-bromo-4'-nitroacetophenone can extend the lifespan of C. elegans.The longest lifespan was obtained when C. elegans was exposed to2-bromo-4'-nitroacetophenone solution at a concentration of 1 μg/mL, indicatingthat C. elegans has a concentration-dependence on food. However, the lifespanwas shortened for mutant daf-16, mutant pmk-1 and mutant pmk-3, indicating thatgenes daf-16, pmk-1 and pmk-3 may be involved in lifespan regulation of C.elegans, and it was concluded that lifespan regulation of C. elegans isachieved via insulin pathway and the P38 pathway.

In addition, it has been found in the studythe lifespan of C. elegans is not only related to itself, but also closelyrelated to its living environment. For example, its lifespan was greatlyshortened if changing the temperature or exposing it to heavy metal ions orPseudomonas aeruginosa, but the lifespan of C.elegans fed with2-bromo-4'-nitroacetophenone was still longer than that of control group,indicating that the compound 2-bromo-4'-nitroacetophenone in C. elegans isheat-stressed, resistant to heavy metals and resistant to Pseudomonasaeruginosa.

In this paper, C. elegans was used as modelorganism to study the molecular mechanism of lifespan regulation by thecompound (2-bromo-4'-nitroacetophenone) for the first time, which not onlybroadens the research scope of lifespan molecular mechanism, but also providesa theoretical basis for investigation of human life.

关键词:秀丽隐杆线虫;寿命;2-溴-4′-硝基苯乙酮,分子机制;抗氧化性

C. Elegans; lifespan; 2-bromo-4

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