Treatment and prevention of shock that uses NF-kB decoy type nucleic acid medicine

休克状态下复苏的主要治疗目标不仅是重建充足的循环，有足够的动脉血压和心输出量，而且要恢复组织灌注和氧合。因此，维持外周循环是一个非常重要的因素。首先，利用兔耳活体显微镜对微血管动力学进行定量研究，我们检测了尿胰蛋白酶抑制剂（UTI）（一种蛋白水解酶抑制剂）对免疫复合物介导的过敏反应期间微血管变化的影响。在全体性过敏性休克中，尿路治疗组的微循环得到了高度的保存，而且尿路治疗组的气道压力也没有增加。其次，我们比较了羟乙基淀粉（HES）和乳酸林格液（LR；对照）对兔失血性休克模型微循环、血流动力学和胶体渗透压的影响，休克是通过去除近一半的循环血容量来诱导的。输注完成后，HES组小动脉直径恢复至基线值的90.8±10.2%，而LR组仅为62.6±10.7% （p<0.005）。HES组动脉血流速度和血流率的恢复也明显优于LR组（p<0.005）。输注完成后HES组平均动脉压、中心静脉压、血浆胶体渗透压均显著高于LR组（p<0.005）。我们得出结论，静脉输注HES可有效维持兔失血性休克模型的微循环、血流动力学和胶体渗透压。核因子-κB （NF-κB）是一种在炎症部位迅速激活的转录因子，因此可能参与了脓毒性休克的进展。目前我们正在研究NF-κB抑制剂是否对感染性休克有效。

The primary therapeutic goal of resuscitation in shock state is not only to reestablish an adequate circulation with sufficient arterial blood pressure and cardiac output, but also to restore tissue perfusion and oxygenation. Maintenance of the peripheral circulation is therefore a very important factor.First, using intravital microscopy of the rabbit ear for quantitative studies of microvascular dynamics, we examined the impact of urinary trypsin inhibitor (UTI), a proteolytic enzyme inhibitor, on microvascular changes during immune complex-mediated anaphylaxis. The microcirculation was highly preserved in the UTI-treated groups during systemic anaphylactic shock Moreover, increased airway pressure was prevented in the UTI-treated group. Second, we compared the effects of hydroxyethyl starch (HES) and lactated Ringer's solution (LR ; control) on the microcirculation, hemodynamics, and colloidal osmotic pressure in a rabbit model of hemorrhagic shock Shock was induced by removing nearly half of the circulating blood volume. After the completion of infusion, arteriolar diameter significantly recovered to 90.8±10.2% of the baseline value in the HES group, as compared with only 62.6±10.7% in the LR group (p<0.005). Recovery of arterial blood flow velocity and blood flow rate was also significantly better in the HES group than in the LR group (p<0.005). Mean arteriolar pressure, central venous pressure, and plasma colloid osmotic pressure after the completion of infusion were significantly greater in the HES group than in the LR group (p<0.005). We conclude that intravenous infusion of HES effectively maintains the microcirculation, hemodynamics, and colloidal osmotic pressure in a rabbit model of hemorrhagic shock Nuclear factor-κB (NF-κB) is a transcription factor that is rapidly activated at the site of inflammation and thus might have been involved in the progression of septic shock. Now we are studying whether an inhibitor of NF-κB is effective for septic shock.