P13K、P38 MAPK及ERK1/2抑制剂对EGF诱导的血管平滑肌细胞迁移的实验研究

目的 探讨P13K抑制剂Wortmannin、P38 MAPK抑制剂SB202190及ERK1/2抑制剂PD98059对表皮生长因子(EGF)诱导的大鼠主动脉平滑肌细胞(VSMCs)迁移的影响.方法 以1%FCS血清孵育为对照,用EGF(10ng/ml)刺激,平行加入PD98059(PD组)、SB202190(SB组)和Wortmannin(WT),划痕损伤实验分析VSMCs迁移情况.结果 划痕后24 h,EGF组VSMCs迁移较对照组明显(P<0.01),WT组、SB组及PD组与EGF组相比都明显抑制VSMCs迁移(P<0.01),但三个抑制剂组之间差异无统计学意义(P>0.05);划痕后30 h,EGF组VSMCs迁移仍较对照组明显(P<0.01),WT组、SB组及PD组与EGF组相比则明显抑制VSMCs迁移(P<0.01),且三个抑制剂组之间差异有统计学意义,其中SB组较WT组和PD组抑制VSMCs的迁移更明显(P<0.01).结论 EGF诱导VSMCs迁移可能通过P13K、P38 MAPK及ERK1/2途径起作用,且P38 MAPK途径作用更明显.

Effects of the inhibitors of PI3K, P38 MAPK and ERK1/2 on the migration of EGF-induced vascular smooth muscle cells

Objective To study the effects of Wortmannin, inhibitor of PI3K and SB202190, inhibitor of P38 MAPK and PD98059, inhibitor of ERK1/2 on the migration of epidermal growth factor (EGF)-induced vascular smooth muscle cells (VSMCs). Methods There were fives groups in this experiment, including control group, EGF group, PD98059 (PD) group, SB202190(SB) group and Wortnannin (WT) group. The migration rate of the VSMCs was measured by wound healing assay. Results At the 24th hours after wounding, there was obvious migration in EGF group compared to control group. The migration of VSMCs was significantly inhibited in PD group, SB group and WT group compared to the EGF group, but there were no significant difference among three inhibitor groups. At the 30th hours after woun-ding, there was still obvious migration in EGF group compared to control group. The migration of VSMCs was significantly inhibited in the three iuhibitors group compared to the EGF group, and there were significant difference among three inhibitor groups. Furthermore, inhibiting effect on VSMCs in SB group was more obvious compared to PD group and WT group. Conclusion These results suggested that the migra-tion of EGF-induced VSMCs may play a role through PI3K, P38 MAPK and ERKI/2 signal pathways, and the effect of P38 MAPK signal pathway is very important.