Abstract:

Objective To explore the influence of bone marrow⁃derived mesenchymal stem cells modified with heme oxygenase⁃1（MSC⁃HO⁃1）on oxidative stress in pulmonary microvascular endothelial cells（PVECs） following lipopolysaccharide（LPS）stimulation. Methods PVECs were divided into group A（PVEC + LPS）， group B（PVEC/MSC+LPS），group C（PVEC/MSC⁃HO⁃1+LPS）and group D（PVEC）. In groups B and C，PVECs were co⁃cultured with MSC or MSC⁃HO⁃1 overnight. LPS（0.1 mg/mL），as a stimulus，was thenadded into transwell co⁃culture system for 6 hours. Intracellular accumulation of ROS was measured using a commercial kit and flow cytometry. Activities of lipid peroxide（LPO），malondialdehyde（MDA），superoxide dismutase（SOD）and gluta⁃ thione peroxidase（GSH⁃PX）in PVECs were determined by using colorimetric assay. HO⁃1 protein expression of PVEC was analyzed by Western blot. Results As compared with group D，LPS⁃stimulation caused the imbalance of oxidative stress in PVECs. Co⁃culture with MSC or MSC⁃HO⁃1 significantly inhibited oxidative stress induced by LPS in PVECs，and the extent of inhibition in group C was more evident. Western blot analysis showed that co⁃ culture with MSC⁃HO⁃1 could significantly upregulate protein expression of HO⁃1 in PVECs. Conclusions MSC⁃ HO⁃1 attenuates lipopolysaccharide⁃induced oxidative stress in PVECs. The detailed mechanism might be associated with upregulation of HO⁃1 expression in PVECs.

Key words:

mesenchymal stem cell, lipopolysaccharide, heme oxygenase?1, oxidative stress, pul?monary microvascular endothelial cell