The effect of m-Nisoldipine on 5-HT-induced proliferation,migration of rat PASMCs and the mechanisms / 中国药理学通报

ABSTRACT

Aim To explore the effect of m-Nisoldipine(m-Nis) on 5-HT-induced proliferation,migration of rat PASMCs and to study the mechanisms.Methods PASMCs were cultured with the explant technique,and were divided into 6 groupscontrol group,5-HT(1 μmol·L~(-1)) group and m-Nis(10~(-5),10~(-6),10~(-7),10~(-8) mol·L~(-1))group.MTT assay was used to evaluate the proliferation of PASMCs,and transwell chambers were used to detect the migration of PASMCs.In addition,the expression of PCNA and the phosphorylation of ERK1/2 were evaluated by Western blot analysis.Results m-Nis inhibited the proliferation(P<0.05 or P<0.01)and migration(P<0.01)of rat PASMCs induced by 5-HT obviously.Similarly,Western blot analysis of PCNA indicated that the expression of PCNA was significantly higher in 5-HT group than that in control group(P<0.01).Whereas,in four m-Nis treated groups,the level of PCNA was markedly decreased(P<0.05 or P<0.01).Meanwhile,m-Nis 10~(-5),10~(-6) and 10~(-7) mol·L~(-1) pretreatment also reduced 5-HT-induced phosphorylation of ERK1/2 obviously(P<0.05 or P<0.01).Conclusion m-Nis inhibits 5-HT-induced proliferation and migration of rat PASMCs obviously,which may be related to the inhibition of PCNA expression and the blockage of ERK1/2/MAPK signal pathway.