Rho激酶和PKC在环孢素A改善休克血管反应性中的作用及与MPTP的关系  

Role of Rho-kinase and PKC in cyclosporine A regulating vascular reactivity and it relationship to MPTP after traumatic hemorrhagic shock

作　　者：雷艳[1] 杨新征 董昭君 

机构地区：[1]第三军医大学卫勤训练基地医学综合教研室,重庆400038 [2]解放军第222医院病理科,吉林吉林132011 [3]第三军医大学军事预防医学院毒理学研究所,重庆400038

出　　处：《局解手术学杂志》2015年第4期355-358,共4页Journal of Regional Anatomy and Operative Surgery

基　　金：国家自然科学基金(81270400)

摘　　要：目的观察Rho激酶和PKC在环孢素A(Cs A)改善创伤失血性休克大鼠血管反应性中的作用及与线粒体通透性转换孔(MPTP)开放的关系。方法采用创伤失血性休克大鼠模型和缺氧培养的血管平滑肌细胞(VMSC),观察了Rho激酶和PKC在Cs A调节休克血管反应性中的作用,以及对血管平滑肌细胞线粒体MPTP开放的影响,同时观察Cs A对休克动物炎症因子TNF-α、IL-1β和IL-6水平的影响。结果 Cs A明显改善了休克血管反应性,Rho激酶抑制剂Y27632可显著拮抗Cs A恢复休克血管反应性的作用,但是PKC抑制剂staurosporine对Cs A的作用无明显影响。Cs A和Rho激酶激动剂U46619都可抑制缺氧后线粒体MPTP的开放程度。休克后大鼠血液中TNF-α和IL-1β的浓度均显著增加,但Cs A处理仅使其轻微减少。结论 Cs A可以通过抑制线粒体MPTP开放改善休克后血管的低反应性,发挥对创伤休克的治疗作用。Rho激酶参与了这其中的调节过程。Objective To investigate the relationship of the beneficial effect of Cs A on vascular reactivity to Rho-kinase,protein kinase C（ PKC） and mitochondrial permeability transition pore（ MPTP） in traumatic hemorrhagic shock rats. Methods With traumatic hemorrhagic shock rats and hypoxia-treated vascular smooth muscle cells（ VSMCs）,the role of Rho-kinase and PKC in Cs A-regulating vascular reactivity following shock and their relationship to MPTP was observed. Meanwhile,the effects of Cs A on inflammatory mediators including TNF-α,IL-1β and IL-6 were also studied. Results Cs A significantly improved the vascular reactivity of superior mesenteric artery following hemorrhagic shock. Rho-kinase inhibitor Y27632 significantly antagonized Cs A-induced increase of vascular reactivity,while PKC inhibitor staurosporine had no significant influences on the effects of Cs A. Further studies showed that Cs A and Rho-kinase agonist U46619 inhibited the opening of MPTP in hypoxia-treated VSMCs. In addition,shock induced a significant increase of TNF-α and IL-1β,but Cs A did not show a significant inhibitory effect on their level. Conclusion Cs A-induced restoration of vascular reactivity following traumatic hemorrhagic shock via inhibiting MPTP opening,and Rho-kinase participate in this process.

关 键 词：线粒体通透性转换孔 环孢素A 血管反应性 创伤失血性休克 RHO激酶 

分 类 号：R605.971[医药卫生—急诊医学]