苦参碱通过上调KLF4/NH2通路减轻H2O2 诱导的人脐静脉内皮细胞氧化损伤.

AIM: To investigate the mechanism and the protective effect of matrine against hydrogen peroxide (H2O2) -induced oxidative injury in human umbilical vein endothelial cells (HUVECs) based on the KLF4/Nrf2 pathway. METHODS: The HUVECs were cultured and screened to determine the experimental concentration of matrine using CCK-8 method. The HUVECs were divided into control group, model group, and low-, medium- and high-concentration (0.5, 1 and 2 mmol/L) matrine groups. An oxidative injury model of HUVECs was induced by H2O2 (0.5 mmol/L), and cell viabilty and intracellular reactive oxygen species (ROS), malondialdehyde(MDA), superoxide dismutase (SOD) and glutathione peroxidase(GPX)levels were detected. The mRNA and protein levels of Kriippel-like factor 4(KLF4), nuclear factor E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), quinone oxidoreductase 1(NQO1) and y-glutamyl cysteine synthetase (y-GCS) were detected using RT-qPCR and Western blot. Changes in these indicators were observed after siRNA-mediated knockdown of KLF4 gene expression and cotreatment with matrine. RESULTS: Compared with model group, the cell viability was increased (P<0. 05), ROS and MDA levels were decreased (PVO. 05), SOD and GPX activity was increased (PVO. 05), and the expression levels of KLF4, NRF2, HO-1, NOQI and y-GCS were increased in matrine groups（PV0. 05）. Inhibiting KLF4 expression significantly weakened the protective effect of matrine against H2O2- induced decrease in cell viability, increase in ROS, and expression of oxidative stress-related molecules（PV0. 05）. CONCLUSION: Matrine can alleviate H2O2-induced oxidative injury in HUVECs by activating KLF4/Nrf2 pathway and inhibiting oxidative stress. [ABSTRACT FROM AUTHOR]