PKC信号通道对严重创伤性休克大鼠血管舒缩功能的调节作用

Role of protein kinase C signaling pathway on vascular contraction and relaxation in severe truamatic shock rats

目的探讨蛋白激酶C(PKC)信号通道是否参与了严重创伤性休克后血管舒缩功能的调控。方法取严重创伤性失血性休克大鼠的腹腔动脉(CA),观察PKC激活剂PMA及PKC抑制剂Staurosporine对休克后去甲肾上腺素(NE)、氯化钾(KC l)诱导的血管收缩反应的影响,以及PMA对乙酰胆碱(ACh)介导的内皮依赖性舒张(EDR)和硝普钠(SNP)介导的内皮非依赖性舒张(EIDR)反应的影响。结果严重创伤性失血性休克大鼠腹腔动脉对NE、KC l诱导的收缩反应以及ACh、SNP介导的舒张反应都显著降低;PMA(0.01、0.1、1μmol/L)对NE、KC l诱导的休克血管收缩反应有显著的增强作用,且呈浓度依赖性;Staurosporine(100 nmol/L)可使休克血管对NE、KC l的反应性进一步降低,同时Staurosporine预处理能显著抑制PMA增强休克血管收缩反应的作用;PMA(0.1μmol/L)可使ACh和SNP诱导的舒张反应都进一步降低。结论PKC信号通道对严重创伤后的血管舒缩功能具有重要的调节作用。

Objective To investigate the modulation of protein kinase C （PKC） signaling pathway on vascular systolic/relaxant function of rats after severe truamatic shock. Methods The celiac artery （CA） rings were isolated from severe truamatic hemorrhagic shock rats and adopted to assay the effect of PMA, an activator of PKC, and Staurosporine, an inhibitor of PKC on the contraction of CA induced by norepi- nephrine （NE） and KCl, and the effect of PMA on the endotheliuim-dependent relaxation （EDR） of CA induced by ACh and on the endothelinm-independent relaxation （EIDR） of CA induced by SNP. Results The contractile response of CA to NE and KCl after severe truamatic hemorrhagic shock was significantly decreased as compared with the normal group, PMA （0.01,0.1,1 μmol/L） pretreatment significantly increased the contractile response of CA to NE and KCl. Staurosporine, the inhibitor of PKC, further decreased the contractile response of CA to NE and KC1 and antagonized PMA-induced increase of vascular contraction. PMA （0.1 μmol/L） significantly decreased the relaxation of CA to ACh and SNP. Conclusion PKC signaling pathway may be have an important role on the regulation of vascular systolic/ relaxant function after severe truamatic shock.