Effect of STAT5 Pathway Inhibitor Pimozide on NO and iNOS Expressions in the Inflammation Model of RAW264.7 Cell / 中国药房

ABSTRACT

OBJECTIVE:To investigate the effect of STAT5 pathway inhibitor pimozide on the expressions of nitric oxide (NO)and nitric oxide synthetase(iNOS)in the model of mouse macrophage RAW264.7 inflammation induced by lipopolysaccha-ride (LPS). METHODS:RAW264.7 cells in logarithmic growth phase were divided into blank control group,drug control group (10μmol/L pimozide),model group(1μg/ml LPS)and the pimozide groups of low,middle and high doses(2.5,5 and 10μmol/L), where the corresponding cells were given pimozide 30 min before the administration of LPS,and then were cultured for 24 h. Griess method was used to determine the content of NO in the supernate of cell culture solutions of all groups,real-time quantita-tive polymerase chain reaction(RT-PCR)to determine iNOS mRNA expression,and Western blot method to determine the protein expression of iNOS and phosphorylated STAT5(p-STAT5). RESULTS:The content of NO,iNOS mRNA and protein expressions and the content of p-STAT5/STAT5 in the cells in the model group were higher than those in the blank control group,with statisti-cally difference (P<0.01). Compared to the model group,the pimozide groups of middle and high doses had lower content of NO,iNOS mRNA and protein expressions and the content of p-STAT5/STAT5 in the cells,with statistically difference(P<0.01 or P<0.05). CONCLUSIONS:STAT5 pathway inhibitor pimozide can inhibit the release of NO by inhibiting iNOS mRNA and pro-tein expressions in cells.