参与失血性休克血管钙敏感性调节的信号分子

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+（3×10-2 mol/L）水平，Emax分别为0.630 g/mg、0.595 g/mg、0.624 g/mg，均明显高于休克组的0.377 g/mg(P<0.05，P<0.01)；fasudil、staurosporine、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+（3×10-2 mol/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。

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

AIM: To observe the regulatory effects of Rho-kinase, PKC and PKG on calcium sensitivity 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 Ca2+ 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 sensitivity 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 Ca2+ shift to the left, their Emax of Ca2+ (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 Ca2+ shift to the right, their Emax at 3×10-2 mol/L of Ca2+ 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.