Dexmedetomidine preconditioning alleviates H2O2-induced oxidative stress and apoptosis in human umbilical vein endothelial cells via p38MAPK signaling pathway

Background: Ischemia-reperfusion injury (IRI) is the main cause of perioperative organ injury, and the morbidity increase constantly in population. Due to a lack of effective treatment, IRI is associated with a high mortality rate. Thus, we need to discover an effective means to alleviate IRI. Methods: : HUVECs were treated with different concentrations of H 2 O 2 alone and in combination with Dex to explore the dose-effect relationship of different concentrations of H 2 O 2 and Dex on HUVEC. In order to explore the relationship between Dex and p38MAPK signal pathway, HUVEC was treated with SB202190, an inhibitor of p38MAPK signal pathway. Cell viability was detected by CCK-8 method. ELISA kit was used to detect lactate dehydrogenase (LDH). Fluorescence probe DCFH-DA staining was used to detect ROS level. Flow cytometry analysis with Propidium Iodide (PI) was used to determine the rate of cell apoptosis. And the protein expression of p-p38MAPK, total p38MAPK, p-ERK1/2 and caspase9 was detected by western blot. Results: : 1）H 2 O 2 could damage HUVEC and lead to the release of LDH. The higher the concentration of H 2 O 2 , the more severe the injury. 2）Dex pretreatment attenuated H 2 O 2 -induced oxidative stress injury and apoptosis of HUVEC. The cell activity of HUVEC increase as Dex concentration increase, the release of LDH decreased, the intracellular ROS level and apoptosis rate decreased, the protein expression of p-p38MAPK and caspase9 decreased, while the protein expression of p-ERK1/2 increased. 3）Dex had the same effect as SB202190, an inhibitor of p38MAPK signaling pathway. After the application of SB202190, the activity of HUVECs increased significantly, while LDH, intracellular ROS and apoptosis rate decreased significantly. Western blot showed that the protein expression of p-p38MAPK and caspase9 decreased significantly, while the protein levels of p-ERK1/2 increased significantly. Conclusion: 1）Dex attenuates H 2 O 2 -induced oxidative stress injury and apoptosis of HUVEC in a concentration-dependent. 2）Dex may attenuate H 2 O 2 -induced oxidative stress injury and apoptosis of HUVEC by inhibiting p38MAPK signal pathway.