参与失血性休克血管钙敏感性调节的信号分子

The signal transducers involved in the regulation of calcium sensitivity of vascular smooth muscle in hemorrhagic shock

目的:观察Rho-激酶、PKC、PKG对失血性休克大鼠血管钙敏感性的调控作用。方法:取失血性休克大鼠肠系膜上动脉,利用离体血管环张力测定技术,用去极化状态下(120 mmol/L K+)血管环对梯度浓度Ca2+的收缩力反映钙敏感性,观察Rho-激酶激动剂血管紧张素Ⅱ(Ang-Ⅱ)、Rho-激酶抑制剂fasudil、PKC激动剂PMA、PKC拮抗剂staurosporine、PKG激动剂8Br-cGMP和PKG拮抗剂KT-5823对失血性休克血管钙敏感性的影响。结果:Ang-Ⅱ、PMA、KT-5823可增高失血性休克血管的钙敏感性,表现为Ca2+的量效曲线明显左移,在Ca2+(3×10-2mol/L)水平,Emax分别为0.630 g/mg0、.595 g/mg0、.624 g/mg,均明显高于休克组的0.377 g/mg(P<0.05,P<0.01);fasudils、taurosporine、8Br-cGMP可降低失血性休克血管的钙敏感性,表现为Ca2+的量效曲线明显右移,在Ca2+(3×10-2mol/L)水平,Emax分别为0.242 g/mg、0.230 g/mg、0.256 g/mg,均显著低于休克组(P<0.05,P<0.01)。结论:Rho-激酶、PKC、PKG对失血性休克大鼠血管钙敏感性有调节作用,Rho-激酶、PKC可上调钙敏感性,PKG可下调钙敏感性。

AIM： To observe the regulatory effects of Rho - kinase, PKC and PKG on calcium semitivity of vascular smooth muscle in hemorrhagic shock in rats. METHODS： The superior mesenteric artery （SMA） from hemorrhagic shock model of rat was adopted to assay the calcium sensitivity via observing the contraction initiated by Ca^2＋ under depolarizing conditions （120 mmol/L K^＋） with isolated organ perfusion system. Rho - kinase agonist Ang -Ⅱ and inhibitor fasudil, PKC agonist PMA and inhibitor staurosporine, PKG agonist 8Br - cGMP and inhibitor KT - 5823 were used as tool .agents to study the regulatory effect of Rho - kinase, PKC and PKG on the calcium semitivity of SMA following shock. RESULTS： Ang-Ⅱ , PMA and KT- 5823 improved the calcium sensitivity of SMA and made the cumulative dose - response curve of SMA to Ca^2＋ shift to the left, their Emax of Ca^2＋ （at 3 × 10^-2 mol/L） was 0.630 g/mg, 0.595 g/mg and 0.624 g/mg, respectively, which were all higher than that in shock control （0.377 g/mg） （ P 〈 0.05, P 〈 0.01）. Fasudil, staurosporine and 8Br - cGMP delimitated the calcium sensitivity of SMA and made the cumulative dose - response curve of Ca^2＋ shift to the right, their Emax at 3 × 10^-2 mol/L of Ca^2＋ was 0.242 g/mg, 0.230 g/mg and 0.256 g/mg, respectively, which were all lower than that in shock control （0.377 g/mg） （ P 〈 0.05, P 〈 0.01 ）. CONCLUSION： Rho-kinase, PKC, PKG play important roles in the regulation of calcium sensitivity of vascular smooth muscle in hemorrhagic shock.