Rac对失血性休克大鼠血管反应性的调节作用

The Effects of Rac on Vascular Reactivity Following Hemorrhagic Shock in Rats

目的探讨Rac在失血性休克大鼠血管反应性调节中的作用。方法采用SD大鼠复制休克模型,取离体血管环,观察休克早期和晚期血管反应性的变化以及Rac激动剂和特异性抑制剂对休克早期和晚期血管反应性的影响;通过酶消化法培养原代血管平滑肌细胞(vascular smoot hmuscle cell,VSMC),采用双室培养方式分别观察VSMC缺氧10min和90min后VSMC对去甲肾上腺素(norepinephrine,NE)的收缩反应性变化,同时观察Rac活性调节剂对缺氧后VSMC收缩反应性的影响。结果在休克早期和短暂缺氧后,离体血管环和VSMC对NE收缩反应性均有所升高,Rac的激动剂血小板衍生生长因子(platelet derived growth factor,PDGF)可部分降低休克早期或短暂缺氧后血管反应性,Rac特异性抑制剂NSC23766可拮抗由PDGF所引起的血管反应性的变化,而在休克晚期或长时间缺氧后,离体血管环和VSMC对NE收缩反应性明显降低,NSC23766对休克晚期或长时间缺氧所致血管反应性降低有升高作用。结论休克后血管反应性呈双相变化,休克早期升高,休克晚期降低,Rac参与了休克血管反应性的调节。

OBJECTIVE To observe the effects of Rac on vascular reactivity following hemorrhagic shock（HS） in rats. METHODS The superior mesenteric artery（SMA） from hemorrhagic shock rats was adopted to assay the vascular reactivity via observing the contraction initiated by norepinephrine（NE） with isolated organ perfusion system. With transwell culture, the contractile response of VSMC to NE after hypoxia （10 min, 90 min, after hypoxia）. Meanwhile, the effect of the PDGF and NSC 23766, Rac activity regulating agents, on vascular reactivity was observed. RESULTS The contractile response of SMA to NE at early shock（ immediate after shock） and VSMC contractility to NE after transient hypoxia （10min after hypoxia） were significantly increased, Rac agonist PDGF the decreased reactivity of SMA and VSMC to NE at early shock or 10 min after hypoxia. The effect of PDGF was abolished by NSC 23766. But in the late period of shock or after prolonged hypoxia, the contractile response of SMA and VSMC to NE was decreased, Rac agonist PDGF had no influence on decreasing vascular reactivity in the later period of shock or after 90 min hypoxia, while its inhibitor NSC 23766 increased the contractile response of SMA and VSMC to NE. CONCLUSION Vascular reactivity is biphasic change following hemorrhagic shock, Rac takes part in the regulation of biphasic vascular reactivity regulation after shock.