蛋白激酶C不同亚型对丙泊酚血管舒张作用的影响

Effects of different protein kinase C isoforms on vasodilation induced by propofol

目的探讨丙泊酚的血管舒张作用与蛋白激酶C(PKC)不同亚型间的关系。方法将SD大鼠胸主动脉环随机分为内皮完整组(n=36)和去内皮组(n=36),每组各分6个亚组:①10 nmol/L Go6976+1×10-6mol/L去甲肾上腺素(NA)+丙泊酚处理组(n=6);②10μmol/L Rottlerin+1×10-6mol/L NA+丙泊酚处理组(n=6);③2μmol/L PKCε-Pseudo(假底物)+1×10-6mol/L NA+丙泊酚处理组(n=6);④2μmol/L PKCθ-Pseudo+1×10-6mol/L NA+丙泊酚处理组(n=6);⑤2μmol/L PKCζ-Pseudo+1×10-6mol/L NA+丙泊酚处理组(n=6);⑥1×10-6mol/L NA+丙泊酚处理组(对照组,n=6)。PKCα抑制剂Go6976,PKCδ抑制剂Rottlerin,PKCζ、θ和ε假底物孵育血管环30 min后,加1×10-6mol/L NA收缩血管环达峰值,每15 min加递增浓度的丙泊酚(1×10-6、5×10-6、1×10-5、5×10-5、1×10-4mol/L),观察血管张力的变化。结果内皮完整时,Go6976、PKCε假底物和PKCθ假底物减小丙泊酚引起的血管舒张幅度,与内皮完整的对照组相比差异有统计学意义(P<0.05);Rottlerin抑制丙泊酚的血管舒张效应,且在1×10-6～5×10-5mol/L丙泊酚作用时将舒张效应转为收缩(P<0.05)。去内皮时,Rottlerin、PKCε假底物和PKCθ假底物分别增大相同浓度丙泊酚作用下的血管舒张幅度,与去内皮对照组相比差异有统计学意义(P<0.05);Go6976和PKCζ假底物分别增大1×10-5～1×10-4mol/L丙泊酚作用下的血管舒张幅度(P<0.05)。结论 PKCα、δ、ε、θ参与了内皮完整时丙泊酚引起的血管舒张。

Objective To investigate the relationship between propofol-induced vasodilation and different protein kinase C(PKC) isoforms. Methods Vascular rings of SD rats were randomly divided into endothelium-intact group(n=36) and endothelium-denuded group(n=36),and each group was divided into 6 subgroups: ①10 nmol/L Go6976+1×10-6 mol/L norepinephrine(NA)+ propofol group(n=6);②10 μmol/L Rottlerin+1×10-6 mol/L NA+propofol group(n=6);③ 2 μmol/L PKCε-Pseudo+1×10-6 mol/L NA+ propofol group(n=6);④2 μmol/L PKCθ-Pseudo+1×10-6 mol/L NA+ propofol group(n=6);⑤2 μmol/L PKCζ-Pseudo+1×10-6 mol/L NA+ propofol group(n=6);⑥1×10-6 mol/L NA+ propofol group(control group,n=6).PKCα inhibitor Go6976,PKCδ inhibitor Rottlerin,PKCζ-Pseudo,PKCθ-Pseudo and PKCε-Pseudo were used to pretreat isolated thoracic aorta rings for 30 min.Then 1×10-6 mol/L NA evoked a steady maximal vasoconstriction,propofol was added in progressively increasing cumulative concentrations at a 15 min interval(1×10-6,5×10-6,1×10-5,5×10-5 and 1×10-4 mol/L),and the changes of vascular tone were observed.Results In endothelium-intact group,compared with endothelium-intact group,Go6976,PKCε-Pseudo and PKCθ-Pseudo inhibited propofol-induced vasodilation(P<0.05).Rottlerin also inhibited propofol-induced vasodilation,and even reversed the effect(1×10-6 to 5×10-5 mol/L propofol)(P<0.05).In endothelium-denuded group,compared with endothelium-denuded control group,Rottlerin,PKCθ-Pseudo and PKCε-Pseudo enhanced propofol-induced vasodilation(P<0.05),and Go6976 and PKCζ-Pseudo enhanced vasodilation induced by 1×10-5 to 1×10-4 mol/L propofol(P<0.05). Conclusion PKCα,PKCδ,PKCε and PKCθ involve in propofol-induced vasodilation in intact endothelium.