黄芪甲苷通过SIRT1/AMPK抑制高糖诱导人脐静脉内皮细胞衰老  

Astragaloside Ⅳ inhibits high glucose-induced human umbilical vein endothelial cell senescence through activation of the SIRT1/AMPK signaling

作　　者：谢利亚 张虹 陆吴霞 孙张弛 XIE Li-ya;ZHANG Hong;LU Wu-xia;SUN Zhang-chi(Department of Pharmacy,Zhejiang Rongjun Hospital,Jiaxing,Zhejiang 314000,China)

机构地区：[1]浙江省荣军医院药剂科,嘉兴314000

出　　处：《浙江中西医结合杂志》2023年第3期225-229,共5页Zhejiang Journal of Integrated Traditional Chinese and Western Medicine

摘　　要：目的研究黄芪甲苷(AS-Ⅳ)在高糖条件下对人脐静脉内皮细胞(HUVECs)的抗衰老作用及其可能机制。方法高糖(60 mmol/L)培养HUVECs 48 h后,用二甲双胍(50μmol/L)或AS-Ⅳ(50μmol/L)作用于HUVECs。48 h后检测细胞活力、活性氧(ROS)含量、衰老相关β半乳糖苷酶(SA-β-gal)活性、白细胞介素-6(IL-6)、SIRT1、AMPK、p53和p21的表达。结果高糖显著增加HUVECs中SA-β-gal活性[(55.02±4.16)%比(3.13±1.65)%,P<0.01],降低细胞存活率[(70.75±7.57)%比100.00%,P<0.01],增加ROS产生[(141.05±16.28)%比100.00%,P<0.01]、p-p53[(1.64±0.17)比(1.01±0.10),P<0.05]和p21[(2.06±0.12)比(1.09±0.12),P<0.05]蛋白水平。此外,高糖还显著降低SIRT1[(0.49±0.13)比(1.04±0.14),P<0.01]和p-AMPK[(0.53±0.22)比(1.11±0.14),P<0.01]的蛋白水平,增加IL-6的分泌[(143.65±10.05)%比(100.09±0.91)%,P<0.05]。AS-Ⅳ(50μmol/L)和二甲双胍(50μmol/L)可逆转高糖对HUVECs的上述毒性作用。结论AS-Ⅳ与二甲双胍类似,在高糖条件下对HUVECs具有抗衰老作用,这可能通过其抗氧化活性和SIRT1途径实现。Objective To detect the anti-aging effect of AstragalosideⅣ(AS-Ⅳ)on human umbilical vein endothelial cells(HUVECs)under a high glucose condition and the underlying mechanism.Methods HUVECs were grown in a HUVECs-specific growth medium supplemented with high glucose(60 mmol/L),metformin(50μmol/L),or AS-Ⅳ(50μmol/L)for 48 h and then assessed for change in cell viability,the reactive oxygen species(ROS),cell senescence-associated β-galactosidase(SA-β-gal)activity,interleukin-6(IL-6),SIRT1,AMPK,p53,and p21 using the corresponding assays.Results HUVECs in high glucose cultures showed a significant increase in SA-β-gal activity(55.02±4.16 vs.3.13±1.65%;P<0.01),ROS production(141.05±16.28 vs.100%;P<0.01),and p-p53(1.64±0.17 vs.1.01±0.10;P<0.05),and p21 expression(2.06±0.12 vs.1.09±0.12;P<0.05),but a decrease in cell viability(70.75±7.57 vs.100%;P<0.01)and expression of SIRT1(0.49±0.13 vs.1.04±0.14;P<0.01)and p-AMPK protein(0.53±0.22 vs.1.11±0.14;P<0.01).Moreover,HUVECs in high glucose cultures also showed an increase in IL-6secretion(143.65±10.05 vs.100.09±0.91%;P<0.05).However,treatment of HUVECs with AS-Ⅳ(50μmol/L)or metformin(50μmol/L)showed a reversal of high glucose-induced toxicity to HUVECs.Conclusion AS-Ⅳpossessed an anti-aging effect on HUVECs under a high glucose condition,similar to that of metformin treatment.At the gene level,such effects were through AS-Ⅳ-antioxidant activity and SIRT1 pathway activation.

关 键 词：黄芪甲苷 SIRT1 人脐静脉内皮细胞 细胞衰老 

分 类 号：R285[医药卫生—中药学]