大蒜素激活SIRT1通路抑制过氧化氢诱导人脐静脉内皮细胞的衰老  

Allicin Inhibits H_2O_2-induced Senescence in Human Umbilical Vein Endothelial Cells through Activation of SIRT1

作　　者：胡惠军[1] 潘勇权 范晓娟[1] 胡雪梅[1] 邹伟文[1] 林小龙[1] 

机构地区：[1]广州医科大学附属惠州医院(惠州市第三人民医院)病理科,广东惠州516002

出　　处：《中国生物化学与分子生物学报》2016年第5期536-543,共8页Chinese Journal of Biochemistry and Molecular Biology

基　　金：广东省医学科研基金(No.A2014810;A2015620);湖南省研究生创新基金(No.CX2013B396);惠州市医学科研基金项目(No.2014Y149;2015Y134)~~

摘　　要：Sirtuin1(SIRT1)活性的异常与血管内皮细胞的衰老密切相关。大蒜素作为一种生物活性分子具有抗氧化、抗炎及调脂作用,然而目前尚未见关于大蒜素与SIRT1的活性调节的报道。本研究旨在阐明大蒜素对过氧化氢(H2O2)诱导人脐静脉内皮细胞(HUVECs)衰老的影响,以及Sirtuin1(SIRT1)在其中的作用。SA-β-gal染色及活性氧检测提示,与对照组相比,大蒜素明显减少H2O2诱导半乳糖苷酶阳性细胞数及活性氧的产生。用Western印迹、MTT、RT-PCR及SIRT1活化检测对SIRT1、p-SIRT1、PAI-1的蛋白质、SIRT1mRNA表达及细胞活力进行检测,结果显示,大蒜素可以逆转H2O2诱导的PAI-1表达的升高、SIRT1磷酸化及活性的降低,并且上调细胞的活力。当采用SIRT1抑制剂NAM处理后,大蒜素的这些作用均被阻断。以上结果表明,大蒜素通过激活SIRT1抑制H2O2诱导的HUVECs ROS的产生、活力的下降及细胞的衰老。Abnormal activity of SIRT1 is closely related to the senescence of vascular endothelial cells. As a bioactive molecule, allicin has antioxidant, anti-inflammatory, and lipid-regulating mechanisms. However, few reports about the relationship of allicin and SIRT1 have been published. The present study aims to elucidate the effect of allicin on the senescence of HUVECs induced by H202 and the role of SIRT1 in it. As revealed by SA-[3-gal staining and reactive oxygen species assays, compared with the control group, allicin significantly reduced the number of H2 02 -induced galactosidase-positive cells and the generation of reactive oxygen species. SIRT1, p-SIRT1, and PAl-1 were detected in protein, SIRT1 mRNA expression, and cell viability through Western blotting, MTT, RT-PCR, and SIRT1 activation assays. Results showed that allicin may reverse the elevated expression of H202-induced PAl-1 and phosphorylation of SIRT1, as well as reduce the abnormal activity and increase the vitality of cells. All these behaviors of allicin were blocked after NAM treatment with an SIRT1 inhibitor. All these results demonstrate that allicin inhibitded the HUVECs from H2Oz-induced oxidative stress, cell activated and senescence via the activation of SIRT1.

关 键 词：大蒜素 沉默信息调节因子2相关酶1 动脉粥样硬化 衰老 

分 类 号：R363.1[医药卫生—病理学]