Endothelial bioreactor system ameliorates multiple organ dysfunction in septic rats.
Endothelial bioreactor system ameliorates multiple organ dysfunction in septic rats.
复制标题
内皮生物反应器系统改善脓毒症大鼠的多器官功能障碍。
DOI：
10.1186/s40635-016-0097-y
复制
发表时间：
2016-12
影响因子：
3.5
通讯作者：
Ding F
中科院分区：
文献类型：
--
作者：
Ma S;Lin Y;Deng B;Zheng Y;Hao C;He R;Ding F
背景内皮细胞是脓毒症治疗的潜在靶点。我们以前研究了一种体外内皮细胞治疗系统，称为内皮生物反应器（EBR），它延长了猪内毒素血症脓毒症的生存时间。为进一步研究EBR对盲肠结扎穿孔（cecal ligation and puncture，CLP）脓毒症大鼠的治疗作用及其可能机制，我们建立了一个微型EBR系统，体外循环先通过微型血液滤过器，分离超滤液（UF），然后将UF通过EBR（含有约2 × 106个生长在微载体上的内皮细胞的1-mL柱）并与内皮细胞相互作用。CLP后18小时，用含有内皮细胞（EBR组）或不含细胞（假EBR组）的体外系统处理大鼠4小时。监测生理生化指标、细胞因子、内皮功能和7天生存时间。在体外，脓毒症大鼠的肺内皮细胞与EBR系统和由此产生的变化，他们的功能monitored.ResultsThe EBR系统改善CLP诱导的脓毒症相比，假EBR系统。CLP后，假治疗组大鼠的7天存活率仅为25.0%，而EBR治疗组的7天存活率增加至57.1%（p= 0.04）。EBR系统对肝、肾功能有保护作用，对肾、肺损伤有改善作用。同时减少肺血管渗漏，减轻肺内炎性细胞尤其是中性粒细胞浸润。EBR在体内外均能降低肺内皮细胞间黏附分子-1的表达和CXCL 1、CXCL 2的分泌，减轻中性粒细胞的黏附和趋化作用。此外，EBR系统降低CD 11b表达和细胞内游离钙水平的外周血中性粒细胞，调制这些中性粒细胞的活化。与假EBR系统相比，该体外内皮治疗可能参与调节肺内皮细胞功能，减少中性粒细胞的粘附和趋化，调节外周血中性粒细胞的活化。
BackgroundThe endothelium is a potentially valuable target for sepsis therapy. We have previously studied an extracorporeal endothelial cell therapy system, called the endothelial bioreactor (EBR), which prolonged the survival time of endotoxemia sepsis in swine. To further study of the therapeutic effects and possible mechanisms, we established a miniature EBR system for septic rats induced by cecal ligation and puncture (CLP).MethodsIn the miniature EBR system, the extracorporeal circulation first passed through a mini-hemofilter, and the ultrafiltrate (UF) was separated, then the UF passed through an EBR (a 1-mL cartridge containing approximately 2 × 106endothelial cells grown on microcarriers) and interact with endothelial cells. Eighteen hours after CLP, the rats were treated for 4 h with this extracorporeal system containing either endothelial cells (EBR group) or no cells (sham EBR group). Physiologic and biochemical parameters, cytokines, endothelial functions, and 7-day survival time were monitored. In vitro, the pulmonary endothelial cells of the septic rats were treated with the EBR system and the resulting changes in their functions were monitored.ResultsThe EBR system ameliorated CLP-induced sepsis compared with the sham EBR system. After CLP, the 7-day survival rate of sham-treated rats was only 25.0 %, while in the EBR-treated group, it increased to 57.1 % (p= 0.04). The EBR system protected the liver and renal function and ameliorated the kidney and lung injury. Meanwhile, this therapy reduced pulmonary vascular leakage and alleviated the infiltration of inflammatory cells in the lungs, especially neutrophils. Furthermore, after the EBR treatment both in vivo and in vitro, the expression of intercellular adhesion molecule-1 and the secretion of CXCL1 and CXCL2 of pulmonary endothelium decreased, which helped to alleviate the adhesion and chemotaxis of neutrophils. In addition, the EBR system decreased CD11b expression and intracellular free calcium level of peripheral blood neutrophils, modulated the activation of these neutrophils.ConclusionsThe EBR system significantly ameliorated CLP-induced sepsis and improved survival and organ functions. Compared with the sham EBR system, this extracorporeal endothelial therapy may be involved in modulating the function of pulmonary endothelial cells, reducing the adhesion and chemotaxis of neutrophil, and modulating the activation of peripheral blood neutrophils.