烧伤休克复苏液最佳钠浓度筛选的实验研究

The excessive release of inflammatory mediators is the main factor which increase vascular permeability and lead to shock in the early stage of severe burn. The data shows that hypovolemic shock fluid resuscitation was performed using the hypertonic sodium solution can obviously reduce the release of inflammatory mediators such as TNF-α, IL-6 and other, compared with the isotonic solution. But the system research on hypertonic sodium solution in burn shock resuscitation has not been reported. We hypothesized that hypertonic sodium resuscitation fluids can more obviously inhibit the release of inflammatory mediator with Na+ concentration increased in a certain range. But it will promote the release of inflammatory mediators and aggravate the injury above a certain range of the Na+ concentration. We found that 200mmol/L hypertonic sodium solution on severely scalded rats fluid resuscitation performed in early stage is good results compared with the sodium lactate Ringer's solution. To this end, we observe the changes of electrolyte, pulmonary vascular permeability, inflammatory mediators, signal transduction pathways and other on severely scalded rats fluid resuscitation performed using different Na+ concentrations of hypertonic sodium solution versus the sodium lactate Ringer's solution on the basis of previous studies, and select the best Na+ concentration of hypertonic sodium resuscitation fluid. The implementation of this project will reveal the mechanism of cell and molecular biology which the hypertonic sodium resuscitation fluids versus the isotonic solution can decrease vascular permeability in the early stage of severe burn. It will provide important basis for the selection of burn shock resuscitation fluid and the modification of shock formula in the future.

炎症介质的过量释放是导致严重烧伤早期血管通透性增加和休克的主要因素。有资料显示，使用高渗钠盐液对低容量性休克进行液体复苏较等渗液能明显减少TNF-α、IL-6等炎症介质的释放，但高渗钠盐液对烧伤休克复苏的系统研究未见报道。我们推测，在一定范围内，随着钠浓度增加，高渗钠盐复苏液对炎症介质释放的抑制作用越明显，但钠浓度超过一定的范围，反而会促进炎症介质的释放，加重损伤。我们的前期研究发现，200mmol/L高渗钠盐液对严重烫伤大鼠早期的复苏具有较好的效果。为此，本项目在前期研究的基础上，采用不同钠浓度的高渗钠盐液对严重烫伤大鼠进行液体复苏，并与乳酸钠林格液相比较，观察电解质、肺微血管通透性、炎症介质、信号转导通路等的变化，以期筛选出最佳钠浓度的高渗钠盐复苏液。本项目的实施将揭示高渗钠盐复苏液降低血管通透性的细胞与分子生物学机制，为今后烧伤休克复苏液的选择与休克公式的修改提供重要的依据

本研究通过采用200mmol/L、300mmol/L、400mmol/L、600mmol/L、800mmol/L、1000mmol/L等不同浓度的高渗钠盐液（HS）和乳酸钠林格液（LR）对严重烫伤（30%TBSA）大鼠液体复苏模型，各组大鼠均在液体复苏后2h、8h和24h处死取血和内脏（肺、肠、肝、肾、心）组织，通过检测血清钠、内脏干湿重、炎症细胞因子（TNF-α、IL-1β和HMGB1）、氧化应激反应、血管内皮细胞通透性以及信号转导通道（p38MAPK以及JNK）等方面的指标，从组织、细胞以及分子生物学多角度探讨不同浓度的高渗钠盐复苏液对严重烫伤大鼠全身以及内脏器官损伤影响的初步机制。首次发现：（1）高渗钠盐复苏液与LR比较，均能防止低钠血症的发生，减轻严重烫伤大鼠伤后的内脏器官水肿并能抑制相关炎性因子的表达以及氧化应激反应，降低血管内皮细胞通透性以及信号传导通道活性表达；（2）不同度的高渗钠盐液复苏液对严重烫伤大鼠的复苏效果有差异，在一定范围内，随着Na+浓度增加，高渗钠盐复苏液对炎症介质释放的抑制作用越明显，但Na+超过一定的浓度，反而起相反作用，加重内脏组织损伤。从200mmol/L到600mmol/L，随着浓度的增加，其抑制相关炎性因子的表达以及氧化应激反应的效果越好，超过600mmol/L，随着浓度的增加，其抑制相关炎性因子的表达以及氧化应激反应的效果越差，但血清钠浓度随着高渗钠盐液复苏液浓度的增加而增大；（3）从200mmol/L到1000mmol/L等6个不同浓度的高渗钠盐液复苏液复苏效果看，最佳的Na+浓度是600mmol/L。本研究初步揭示了高渗钠盐复苏液减轻严重烫伤大鼠内脏组织损伤的细胞与分子生物学机制，证实了“在一定范围内，随着Na+浓度增加，高渗钠盐复苏液对炎症介质释放的抑制作用越明显，但Na+超过一定的浓度，反而起相反作用”的假说，初步筛选出了最佳Na+浓度的高渗钠盐复苏液，为今后烧伤休克复苏液的选择与休克公式的修改提供了重要的参考依据。