【摘要】 目的探讨血管紧张素-(1-7)[Ang-(1-7)]能否通过抑制糖原合成酶激酶-3β(GSK-3β)通路对抗高糖引起的人脐静脉内皮细胞(HUVECs)凋亡及炎症。方法应用高糖(HG,40 mmol/L葡萄糖)处理HUVECs 24 h建立HG损伤细胞模型。应用CCK-8法测定细胞存活率;Western blot法检测蛋白的表达水平;ELISA法检测白细胞介素-1β(IL-1β)和肿瘤坏死因子-α(TNF-α)水平。结果应用HG处理HUVECs 24 h能引起细胞存活率降低,cleaved caspase-3表达水平和炎症因子(包括IL-1β和TNF-α)分泌水平升高及激活GSK-3β;20μmol/L Ang-(1-7)与HG共处理HUVECs 24 h能抑制HG引起的细胞毒性、cleaved caspase-3表达和炎症因子分泌增多及GSK-3β激活。Mas受体[为Ang-(1-7)受体]抑制剂A-779能减弱上述的Ang-(1-7)的抗细胞凋亡、抗炎症及对GSK-3β的抑制作用;GSK-3β抑制剂能减轻HG引起的HUVECs凋亡及炎症因子分泌增多。结论 Ang-(1-7)/Mas受体轴可通过抑制GSK-3β通路保护HUVECs对抗HG引起的细胞凋亡及炎症反应。更多还原

【Abstract】 Objective To explore whether angiotensin-(1-7)[Ang-(1-7)]protected against the high glucose(HG)-induced cellular apoptosis and inflammation by inhibiting glycogen synthase kinase-3β(GSK-3β)pathway in vascular endothelial cells. Methods Human umbilical vein endothelial cells(HUVECs)were treated with 40 mmol/L glucose(high glucose,HG)for 24 h to established a model of cell injury. Cell viability of HUVECs was tested by cell counting kit 8(CCK-8)assay;The protein expression level was examined by western blot assay. The secretion levels of IL-1β and tumor necrosis factor-α(TNF-α)were measured by the ELISA kit. Results Treatment of HUVECs with HG for 24 h induced a decrease in cell viability,increases in the expression level of cleaved caspase 3 and the secretion level of cytokine,including IL-1β and TNF-α,and activation of GSK-3β. Cotreatment of HUVECs with 20 μmol/L Ang-(1-7)and HG for 24 h attenuated the HG-induced cytotoxicity,increases in cleaved caspase 3 expression and the secretion level of cytokine,and activation of GSK-3β. A-779,a Mas receptor[as Ang-(1-7)receptor]inhibitor ameliorated the Ang-(1-7)-induced anti-apoptosis,anti-inflammation and inhibition of GSK-3β activity,mentioned above. LiCl,an inhibitor of GSK-3β also alleviated the HG-induced apoptosis and an increase in the level of cytokine secretion. Conclusion Ang-(1-7)/Mas receptor axis protects HUVECs against the HG-induced apoptosis and inflammatory response.更多还原