Scutellarin antagonizes ischemia-reperfusion injury to human cardiac microvascular endothelial cells by increasing ERK phosphorylation / 医学研究生学报

ABSTRACT

Objective Scutellarin (SCU), a Chinese traditional medicine, has a protective effect against ischemia-reperfusion (IR) induced myocardial injury, but it is not yet clear whether SCU acts against vascular endothelial IR injury via extracellular signal-regulated kinase 1/2 (ERK1/2).The aim of this study was to explore the effect of SCU on hypoxia-reoxygenation (HR)-induced injury to human cardiac microvascular endothelial cells (HCMECs) and its influence on the ERK1/2 signaling pathway.Methods HCMECs were subjected to normal culture and divided into a normal control, a DMSO, an SCU 1 μmol/L, and an SCU 10 μmol/L group.The model of HR injury was established by exposing the HCMECs to 12-h hypoxia and 12-h reoxygenation after treated with DMSO or SCU at 1 and 10 μmol/L for 2 hours.Then, the survival rate of the HCMECs was detected by MTT and trypan blue staining, the concentration of malondialdehyde (MDA) in the cells measured, and the expressions of the p-ERK1/2, ERK2 and GAPDH proteins determined by Western blot.Results SCU at 1 and 10 μmol/L significantly increased the survival rate of the normally cultured HCMECs ([110.40±2.34] and [122.00±1.25] ％) as compared with that of the normal control (100％) (P<0.05), while HR injury markedly decreased the vitality of the HCMECs ([68.00±4.06] ％) in comparison with that of the blank control (100％) (P<0.05).The survival rate of the HCMECs was remarkably higher in the HR+SCU 1 μmol/L and HR+SCU 10 μmol/L groups than in the HR model group ([90.53±3.67] and [92.04±2.32] ％) (P<0.05), and so was their vitality in the SCU 10 μmol/L group than in the normal control ([96.78±2.01] vs [90.06±1.85] ％, P<0.01), while their survival rate was significantly lower in the HR model than in the blank control ([73.72±4.91] vs [91.83±2.34] ％, P<0.01) and remarkably higher in the SCU 10 μmol/L ([87.59±2.64] ％) than in the HR model group (P<0.05).The MDA concentration in the HCMECs was markedly increased in the HR model and HR+DMSO groups as compared with the blank control (P<0.01), but decreased in the HR+SCU 1 μmol/L and HR+SCU 10 μmol/L groups in comparison with the HR model group (P<0.05).The expression of the p-ERK1/2 protein was significantly down-regulated in the HR model group as compared with the blank control (P<0.01), but up-regulated in the HR+SCU 10 μmol/L group in comparison with the HR model (P<0.01).Conclusion HR injury reduces the vitality of HCMECs, increases the MDA concentration, and down-regulates the expression of the p-ERK1/2 protein in HCMECs, while SCU acts against ischemia-reperfusion injury to HCMECs by increasing ERK phosphorylation.