Kao N Raymond L C, Xenocostas Anargyros, Driman David K, Rui Tao, Huang Weixiong, Jiao Xiujun, Martin Claudio M
Canadian Forces Health Services, Department of National Defence, Ottawa, Ontario, Canada.
J Trauma. 2011 Nov;71(5 Suppl 1):S456-61. doi: 10.1097/TA.0b013e318232e782.
Gut injury and bacterial translocation develop and persist after limited periods of hemorrhagic shock. Erythropoietin (EPO) can exert hemodynamic, anti-inflammatory, and tissue protective effects. We tested the hypothesis that EPO given at the time of resuscitation with saline will reduce functional ileal injury 24 hours after shock.
Sprague-Dawley rats (n = 6 per group) were randomized to sham surgery or hemorrhagic shock maintained at mean arterial pressure 40 mm Hg for 60 minutes and then treated with either saline resuscitation (three times the volume of shed blood) or saline + recombinant human EPO (rHuEPO) resuscitation. Intravenous rHuEPO (1,000 U/kg) was given at the start of saline resuscitation, and at 24 hours ileal function was evaluated using quantitative cultures of mesenteric lymph nodes to assess for bacterial translocation (colony-forming units per gram of tissue [CFU/g]), determination of portal vein plasma endotoxin levels and histopathological evaluation using semi-thin plastic sections of the distal ileum. In a second series of animals, fluorescein isothiocyanate-dextran 4000 (FD-4) was used to assess mucosal permeability of the distal ileum to macromolecules.
At 24 hours, the saline group had morphologic evidence of intestinal injury when compared with the sham group, and the degree of mucosal injury was less in the saline + rHuEPO when compared with the saline group, which demonstrated significantly reduced bacterial translocation to the mesenteric lymph nodes (383 CFU/g ± 111 CFU/g vs. 1130 CFU/g ± 297 CFU/g; p < 0.05) and decreased terminal ileum permeability to FD-4 (3.08 μg/mL ± 0.31 μg/mL vs. 5.14 μg/mL ± 0.88 μg/mL; p < 0.05). No significant difference was found in the portal vein endotoxin levels between the two groups. Histopathological evaluation demonstrated a trend for decreased enterocyte disarray or disruption and vacuolization in the saline + rHuEPO versus saline group.
Using rHuEPO at time of saline resuscitation resulted in decreased bacterial translocation and permeability to macromolecules 24 hours after shock. These observations suggest that rHuEPO can mediate a protective effect on intestinal mucosal barrier function during ischemic injury.
在有限时长的失血性休克后，肠道损伤和细菌易位会出现并持续存在。促红细胞生成素（EPO）可发挥血流动力学、抗炎及组织保护作用。我们检验了以下假设：在以生理盐水复苏时给予EPO可减轻休克后24小时的回肠功能损伤。
将Sprague-Dawley大鼠（每组n = 6）随机分为假手术组或失血性休克组，将失血性休克组大鼠平均动脉压维持在40 mmHg 60分钟，然后分别用生理盐水复苏（失血量的3倍体积）或生理盐水 + 重组人促红细胞生成素（rHuEPO）复苏。在生理盐水复苏开始时静脉给予rHuEPO（1000 U/kg），24小时后，通过肠系膜淋巴结定量培养评估细菌易位（每克组织的菌落形成单位[CFU/g]）、测定门静脉血浆内毒素水平，并使用回肠末端半薄塑料切片进行组织病理学评估，以此来评价回肠功能。在第二组动物实验中，使用异硫氰酸荧光素葡聚糖4000（FD-4）评估回肠末端对大分子的黏膜通透性。
24小时时，与假手术组相比，生理盐水组有肠道损伤的形态学证据，与生理盐水组相比，生理盐水 + rHuEPO组的黏膜损伤程度较轻，表现为细菌易位至肠系膜淋巴结显著减少（383 CFU/g ± 111 CFU/g对1130 CFU/g ± 297 CFU/g；p < 0.05），回肠末端对FD-4的通透性降低（3.08 μg/mL ± 0.31 μg/mL对5.14 μg/mL ± 0.88 μg/mL；p < 0.05）。两组门静脉内毒素水平无显著差异。组织病理学评估显示，与生理盐水组相比，生理盐水 + rHuEPO组肠上皮细胞排列紊乱或破坏及空泡化有减轻趋势。
在生理盐水复苏时使用rHuEPO可使休克后24小时细菌易位及对大分子的通透性降低。这些观察结果表明，rHuEPO在缺血性损伤期间可介导对肠黏膜屏障功能的保护作用。
