1-硝基芘通过自噬通路对秀丽隐杆线虫寿命的影响研究

Effects of 1-nitropyrene on lifespan of Caenorhabditis elegans through autophagy pathway

目的 本研究采用秀丽隐杆线虫(简称线虫)模型探讨1-硝基芘(1-nitropyrene,1-NP)对线虫寿命的影响和自噬在寿命影响中的作用。方法 在正常培养条件下,研究不同浓度的1-NP(0、10^(-4)、10^(-2)、10^(2)、10^(4)ng/L)亚急性干预5天对线虫寿命的影响,观察1-NP对线虫健康相关参数如体长、运动能力和脂褐素和寿命的影响。使用实时定量聚合酶链反应(quantitative real time-polymerase chain reaction,qRT-PCR)检测自噬相关标志基因(bec-1和lgg-1)的表达情况。结果 与对照组相比,1-NP可显著降低线虫的寿命,其中104ng/L剂量降低寿命效果最明显,降低率为28.2%。1-NP(10^(4)ng/L)可降低线虫的体长(P<0.05)和自噬关键基因表达水平(P<0.05),增加线虫体内脂褐素的蓄积(P<0.05)。结论 1-NP可以通过降低线虫体内自噬水平,进而使线虫的寿命缩短。

Objective By using the Caenorhabditis elegans model(hereafter referred to as C.elegans),to investigate the effects of 1-nitropyrene(1-NP)on the lifespan of C.elegans and the role of autophagy in the impact of lifespan.Methods The effects of subacute exposure(five days)of 1-NP(0,10^(-4),10^(-2),10^(2),10^(4) ng/L)on the life span of C.elegans were studied under normal culture conditions.The effects of 1-NP on health indicators(body length,exercise capacity and lipofuscin)and longevity of C.elegans were observed.The expression of autophagy related marker genes(bec-1 and lgg-1)was detected by quantitative real time-polymerase chain reaction(qRT-PCR).Results Compared with the control group,1-NP could significantly reduce the lifespan of C.elegans,and 104 ng/L group had the most significant effect,with a reduction rate of 28.2%.1-NP(10^(4) ng/L)decreased the body length of C.elegans(P<0.05)and the expression levels of key autophagy genes(bec-1 and lgg-1))(P<0.05),increased lipofuscin accumulation in C.elegans(P<0.05).Conclusion1-NP can shorten the lifespan of C.elegans by decreasing the autophagy level in C.elegans.