伊拉兔肌内磷脂n—3多不饱和脂肪酸体外抗肿瘤功效及作用机理

摘 要：根据之前的研究成果体外模拟伊拉兔肌内磷脂n-3 多不饱和脂肪酸（polyunsaturated fatty acids，PUFAs）的组成，并研究其功能特性。结果表明：采用噻唑蓝法对复合n-3 PUFAs作用的敏感细胞进行筛选，证实伊拉兔肌内磷脂n-3 PUFAs在30～180 μmol/L劑量范围对HepG2、MV3和A375肿瘤细胞的生长均有抑制作用，且HepG2细胞对复合肌内磷脂n-3 PUFAs的敏感度最高；HepG2的细胞形态及数量变化与复合n-3 PUFAs呈现明显的时效和量效关系；采用膜联蛋白V-异硫氰酸荧光素和碘化丙啶双染法对肿瘤细胞进行凋亡检测，证实伊拉兔肌内复合磷脂n-3 PUFAs的凋亡作用；进一步研究发现，复合n-3 PUFAs及其单体（α-亚麻酸、二十碳五烯酸、二十二碳五烯酸和二十二碳六烯酸）均能够引起HepG2细胞内氧化应激的改变，它们通过显著上调细胞内丙二醛的累积量以及活性氧的相对荧光强度水平，同时下调超氧化物歧化酶的活力实现对HepG2细胞的诱导凋亡作用，其中二十二碳六烯酸在非酶促氧化反应中发挥主要作用，这是肌内磷脂n-3 PUFAs诱导HepG2细胞凋亡的机制之一。

关键词：伊拉兔；肌内磷脂；n-3多不饱和脂肪酸；抗肿瘤；脂质过氧化

Abstract： As an extension of our previous work， the composition of n-3 polyunsaturated fatty acids （PUFAs） in intramuscular phospholipids of Hyla rabbit was simulated in vitro to evaluate their functional characteristics. The sensitivity of various tumor cells to the formulation was tested by the methyl thiazolyl tetrazolium method. It turned out that the formulation at doses in the range of 30–180 μmol/L repressed the growth of HepG2， MV3 and A375 tumor cells， HepG2 cells being most sensitive to the formulation. The formulation affected the morphology and quantity of HepG cells in a time- and dose-dependent manner and it induced apoptosis in the tumor cells as determined by Annexin V-fluorescin isothiocyanate and propidium iodide double staining kit. Furthermore， the formulation and the individual PUFAs （α-linolenic acid， eicosapentaenoic acid， docosapentaenoic acid， and docosahexenoic acid （DHA）） could alter oxidative stress in HepG cells and their apoptosis-inducing activity was associated with a significant increase in cellular malondialdehyde accumulation and the relative fluorescence intensity of reactive oxygen species and with a decrease in superoxide dismutase activity. In addition， DHA played a major role in the non-enzymatic oxidation reaction.

Keywords： Hyla rabbit； intramuscular phospholipids； n-3 polyunsaturated fatty acids； anticancer effect； lipid peroxidation

DOI：10.7506/rlyj1001-8123-201804002

中图分类号：TS201.4 文献标志码：A 文章编号：1001-8123（2018）04-0007-07

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