THE REGULATION OF GLYCOGEN SYNTHASE KINASE-3Β ON THE MESENCHYMAL STEM CELL THERAPY IN THE LYPOPOLYSACCHARIDE INDUCED ACUTE LUNG INJURY IN RAT

Abstract

Acute lung injury (ALI) is a one of severe manifestation and remains a major cause of morbidity and mortality in critically ill patients. Mesenchymal stem cell (MSCs) based therapy is a promising and novel treatment, it has been considered to be a potential treatment of acute lung injury. Glycogen synthase kinase-3β (GSK-3β) has been associated with the pathogenesis of several diseases, that can be a potential therapeutic target. In the current study, we were focused on the possible enhancement, regulatory mechanism of MSCs therapy, what improves the outcome of cell treatment, so that we explored the role of inhibiting GSK-3β with a selective inhibitor of LiCl during treatment of MSCs in the acute lung injury, in vivo. Experiments were carried out on 40 adults, Sprague-Dawley (SD) rats, those were randomly classified into 4 groups: 1. Control group (treated with normal saline (NS) 5 mg/kg), n = 10. 2. Acute lung injury (ALI) group (treated with lypopolysaccharide (LPS) 15 mg/kg), n = 10. 3. ALI+ MSCs group (treated with MSCs via tail vein, after LPS administration 2 h) n = 10. 4. ALI+ MSCs + Lithium chloride (LiCl) group (treated with MSCs and LiCl 20 mg/kg after LPS administration 2 h). The blood serum was collected at 12 h to determine inflammatory cytokines, lung tissues were harvested and analyzed on the 7th and 14th day of study. It was revealed that MSCs with inhibition of GSK-3β (LiCl) treatment group was more effectively suppressed systemic inflammation, inflammatory cell infiltration in lung tissue, pulmonary edema, pathological impairment and protect pulmonary epithelial cells in the acute phase of acute lung injury. In conclusion, in the present study suggested that inhibition of GSK-3β likely to play an enhancement role to improve outcome of MSCs treatment in the acute phase of acute lung injury in vivo.