取代短链脂肪酸对秀丽隐杆线虫的抗氧化作用

Effect of Anti-Oxidant Property of Short Branched-Chain Fatty Acids in Caenorhabditis elegans

短链脂肪酸(short chain fatty acids, SCFAs)是碳原子数为1～6的有机脂肪酸,不但可以作为生物体内能源物质,而且还具有抗炎、影响肠道菌群代谢和预防早发1型糖尿病等重要作用。然而,目前多数是对传统短链脂肪酸的生物学作用进行研究,对取代短链脂肪酸(short branched-chain fatty acids, SBCFAs)的相关研究甚少。本研究以秀丽隐杆线虫为模式动物,系统探究SBCFAs的抗氧化生物活性作用。采用胡桃醌氧化应激模型,在体内评价SBCFAs对秀丽隐杆线虫生存能力的影响,并通过体外抗氧化及H_2DCFDA荧光染色实验,进一步评价SBCFAs清除活性氧自由基(reactive oxygen species,ROS)的能力。本研究证实,在氧化应激研究中,传统脂肪酸不能延长秀丽隐杆线虫的存活时间,而2′-甲基取代短链脂肪酸(n=4-6)具有显著的抗氧化作用。体外抗氧化实验表明,2′-甲基取代短链脂肪酸(n=4-6)不具有体外直接清除ROS的能力,但是H_2DCFDA荧光染色实验显示2′-甲基丁酸能够显著降低线虫体内的ROS水平,表明2′-甲基丁酸通过降低体内ROS水平,从而增强秀丽隐杆线虫的抗氧化应激能力。本研究提示,传统短链脂肪酸不具有抗氧化作用;2′-甲基取代短链脂肪酸(n=4-6)能显著增强秀丽隐杆线虫的抗氧化能力;甲基取代位置和取代烷基长度对短支链脂肪酸的抗氧化作用至关重要,其作用机制需进一步研究。

The short chain fatty acids (SCFAs) are saturated aliphatic fatty acids with no more than six carbon atoms, which are well studied bioactive molecules with anti-inflammatory activities. They affect the metabolism of intestinal flora and prevent the development of early type 1 diabetes. However, there are few studies of SCFAs with branched chain. In this study, juglone was used as oxidant to evaluate the anti- antioxidant effect of short branched chain fatty acids (SBCFAs) by model organism of Caenorhabditis elegan (C. elegan). The results showed that SCFAs had no anti-oxidant activities, while 2′-methyl substituted SCFAs (n=4-6) have significant anti-oxidant activities in C. elegans. 2′-Methyl substituted SCFAs (n=4-6) could not scavenge the reactive oxygen species (ROS) in vitro. However, 2′-Methyl-butyric acid could reduce the endogenous ROS level of C. elegans. Consequently, the anti-oxidant activities of 2′-methyl substituted SCFAs (n=4-6) in C. elegans rely on their actions in vivo. The position of methyl substitution and the length of substituted alkyl groups were critical for the antioxidant activity of short-branched fatty acids. Further mechanistic investigation is ongoing.