ABSTRACT
AIM:To investigate the effects of losartan on lipopolysaccharide (LPS)-induced glial fibrillary acidic protein (GFAP) expression,and to determine whether adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) activation is involved in the mechanism.METHODS:Adult male KM mice were divided into control group,LPS model group,losartan treatment group,and losartan and Compound C co-treatment group.To establish a model of central nervous system inflammation,the mice received daily intracerebroventricular injection of LPS (24 μg/d) for 2 d.Daily losartan administration (0.5,1 or 5 mg · kg-1 · d-1,ip) initiated at 14 d prior to LPS injection.Compound C (10 mg/kg,ip),a selective AMPK inhibitor,started to be injected daily at 2 d prior to LPS injection.The hippocampal tissues in each group were isolated at 3 d after the last LPS injection,and then the protein levels of GFAP,AMPK,p-AMPK,mammalian target of rapamycin (mTOR) and p-mTOR were determined by Western blot.RESULTS:Twice LPS injections significantly increased the expression of GFAP in the hippocampus (P ＜ 0.01).Losartan inhibited LPS-induced GFAP expression in a concentration-dependent way,and losartan at 5 mg· kg-1 · d-1 significantly inhibited GFAP expression and AMPK activation (P ＜ 0.05),but it had no obvious effect on mTOR activation.Furthermore,Compound C significantly reversed the effect of losartan treatment on LPS-induced GFAP expression and AMPK phosphorylation (P ＜ 0.05).CONCLUSION:Losartan inhibits LPS-induced GFAP expression in the mouse hippocampus,and AMPK activation but not mTOR,is involved in the mechanism.
ABSTRACT
AIM:To investigate the effects of losartan on lipopolysaccharide (LPS)-induced glial fibrillary acidic protein (GFAP) expression,and to determine whether adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) activation is involved in the mechanism.METHODS:Adult male KM mice were divided into control group,LPS model group,losartan treatment group,and losartan and Compound C co-treatment group.To establish a model of central nervous system inflammation,the mice received daily intracerebroventricular injection of LPS (24 μg/d) for 2 d.Daily losartan administration (0.5,1 or 5 mg · kg-1 · d-1,ip) initiated at 14 d prior to LPS injection.Compound C (10 mg/kg,ip),a selective AMPK inhibitor,started to be injected daily at 2 d prior to LPS injection.The hippocampal tissues in each group were isolated at 3 d after the last LPS injection,and then the protein levels of GFAP,AMPK,p-AMPK,mammalian target of rapamycin (mTOR) and p-mTOR were determined by Western blot.RESULTS:Twice LPS injections significantly increased the expression of GFAP in the hippocampus (P ＜ 0.01).Losartan inhibited LPS-induced GFAP expression in a concentration-dependent way,and losartan at 5 mg· kg-1 · d-1 significantly inhibited GFAP expression and AMPK activation (P ＜ 0.05),but it had no obvious effect on mTOR activation.Furthermore,Compound C significantly reversed the effect of losartan treatment on LPS-induced GFAP expression and AMPK phosphorylation (P ＜ 0.05).CONCLUSION:Losartan inhibits LPS-induced GFAP expression in the mouse hippocampus,and AMPK activation but not mTOR,is involved in the mechanism.