Effect of chrysophanol on down-regulated expression of c-fos and c-jun mRNA in mouse astrocytes exposed to ammonia and related mechanisms / 中国药理学与毒理学杂志

ABSTRACT

OBJECTIVE To investigate the effect and mechanisms of chrysophanol on the expression of c-fos and c-jun mRNA induced by ammonia chloride(NH4Cl) in mouse astrocytes. METHODS Primary mouse astrocytes were cultured with NH4Cl 5 mmol·L-1+chrysophanol 0.1,1.0 or 10.0 mg·L-1 ,or NH4Cl 5 mmol · L- 1+extracellular regulated kinase1/2(ERK1/2) inhibitor UO126 10 mmol · L- 1 and NH4Cl 5 mmol · L-1+p38 mitogen-activated protein kinase(p38 MAPK)inhibitor SB239063 10 mmol · L-1 for 48 h. The levels of glutathione peroxidase(GSH-Px),superoxide dismutase(SOD),malondaldehyde(MDA), nitric oxide(NO)and nitric oxide synthase(NOS)were detected by UV spectrophotometry. The phos?phorylation levels of ERK1/2 and p38 MAPK were detected by Western blotting. The expression of c-fos and c-jun mRNA was detected by RT-PCR. RESULTS Compared with NH4Cl 5 mmol · L- 1 group, ammonia-induced astrocytes oxidative stress was improved by chrysophanol (1.0 and 10.0 mg · L-1). The content of MDA and NO and the activity of NOS were reduced(P<0.05). The activity GSH-Px and SOD was increased(P<0.05). The phosphorylation level of ERK1/2 and p38 MAPK induced by ammonia was reduced in chrysophanol groups (P<0.05). Ammonia-induced c-fos and c-jun mRNA expression downregulation was reversed by chrysophanol (0.1,1.0 and 10.0 mg · L-1)and UO126 and SB239063(P<0.05). CONCLUSION Chrysophanol may improve the downregulated expresion of c-fos and c-jun mRNA in mouse astrocytes exposed to NH4Cl by anti-oxidative stress by inhibiting the ERK1/2 and p38 MAPK phosphorylation.