静脉复苏联合丙酮酸盐腹腔复苏对失血性休克大鼠肠缺血再灌注损伤的保护作用与机制研究

Studies confirm that direct peritoneal resuscitation with pyruvate-peritoneal dialysis solution following intravenous resuscitation has a great protection on organs and cells, and improves hypoperfusion and dysfunction of abdominal organs after hemorrhagic shock. Our previous researches showed that direct peritoneal resuscitation with pyruvate-peritoneal dialysis solution following intravenous resuscitation alleviated intestinal injury, lactic acidosis and hypoxia from hemorrhagic shock in rats. Mechanisms of action might include the elimination of free oxygen radicals, reduction of neutrophil infiltration, inhibition of the inflammatory response and regulation of intestinal mucosal barrier function. Hereby, we make this research whether and how it protect intestinal ischemia-reperfusion injuries from hemorrhagic shock by direct peritoneal resuscitation with pyruvate following intravenous resuscitation in rats. We will make a research on the effect of different resuscitation methods on intestinal ischemia-reperfusion injuries by making hemorrhagic shock model in rats, reveal the protection against intestinal ischemia-reperfusion injuries from hemorrhagic shock by direct peritoneal resuscitation with pyruvate-peritoneal dialysis solution following intravenous resuscitation, and clarify the mechanism involves the inhibition of JAK/STAT signal path. That includes inhibition oxidative stress response, reduction of the inflammatory response, basification of blood, reduction of apoptosis, protection of intestinal mucosal barrier function. And that will provide new ideas for fluid therapy of hemorrhagic shock on clinic.

研究证实在静脉复苏基础上联合丙酮酸盐腹腔复苏具有良好的器官及细胞保护作用，能够改善失血性休克后腹腔器官的低灌注及功能失调。前期研究发现，对于失血性休克大鼠，静脉复苏联合丙酮酸盐腹腔复苏显著减轻了肠道损伤，改善了大鼠体内乳酸酸中毒及缺氧情况。其机制可能包括清除氧自由基，减少中性粒细胞浸润，抑制炎性反应，保护肠屏障功能。据此提出静脉联合丙酮酸盐腹腔复苏对肠缺血再灌注损伤是否具有保护作用且如何发挥作用的科学问题，通过制备失血性休克大鼠模型，采用静脉复苏联合丙酮酸盐腹腔复苏并与乳酸盐对比，进行不同复苏方式对肠缺血再灌注损伤疗效的研究，揭示丙酮酸盐腹腔复苏对失血性休克大鼠肠缺血再灌注损伤的保护作用，阐明其机制与抑制JAK/STAT通路有关，其作用包括抑制氧化应激反应、减轻炎症反应、碱化血液、减轻细胞凋亡、保护肠屏障功能等，为临床上失血性休克的液体治疗提供新的思路。

已有研究证实在静脉复苏基础上联合丙酮酸盐腹腔复苏具有良好的器官及细胞保护作用，能够改善失血性休克后腹腔器官的低灌注及功能失调。前期研究发现，对于失血性休克大鼠，静脉复苏联合丙酮酸盐腹腔复苏显著减轻了肠道损伤，改善了大鼠体内乳酸酸中毒及缺氧情况。其机制可能包括清除氧自由基，减少中性粒细胞浸润，抑制炎性反应，保护肠屏障功能。据此提出静脉联合丙酮酸盐腹腔复苏对肠缺血再灌注损伤是否具有保护作用且如何发挥作用的科学问题。本项目通过制备失血性休克大鼠模型，采用静脉复苏联合丙酮酸盐腹腔复苏并与乳酸盐对比，进行了不同复苏方式以及不同浓度丙酮酸盐腹膜透析液对肠缺血再灌注损伤疗效的研究。结果显示，丙酮酸盐腹腔复苏组相关血流动力学，血气分析，病理学，氧化应激，炎性反应，凋亡，肠黏膜屏障蛋白指标等均优于乳酸盐腹腔复苏组。证实了静脉复苏联合丙酮酸盐腹腔复苏对失血性休克大鼠肠缺血再灌注损伤具有保护作用，改善了大鼠血流动力学与体内酸碱平衡，纠正了内环境稳态，抑制了炎症反应，增强了系统免疫状态，调节了肠上皮渗透性，维持了肠黏膜屏障功能。且较高浓度丙酮酸盐腹膜透析液具有更好的保护作用。静脉复苏联合丙酮酸盐腹腔复苏对失血性休克大鼠肠缺血再灌注损伤的保护作用机制可能与抑制JAK/STAT通路有关，其相关病理生理和免疫学过程可能包括抑制氧化应激，减少中性粒细胞浸润，改善微循环，抑制凋亡。本研究结果为临床上失血性休克的液体复苏提供了一个新的治疗方向和思路。