乳脂肪球表皮生长因子因子 8 可减轻实验动物失血性休克后的炎症和组织损伤。
Milk fat globule epidermal growth factor-factor 8 mitigates inflammation and tissue injury after hemorrhagic shock in experimental animals.
机构信息
Department of Surgery, Hofstra North Shore-LIJ School of Medicine, Manhasset, New York 11030, USA.
出版信息
J Trauma Acute Care Surg. 2012 Apr;72(4):861-9. doi: 10.1097/TA.0b013e318249a97c.
BACKGROUND
Insufficient clearance of apoptotic cells leads to increased inflammation and exaggerated organ injury. The opsonizing protein, milk fat globule epidermal growth factor-factor 8 (MFG-E8), upregulates apoptotic cell clearance. The purpose of this study was to determine the degree of apoptotic cell clearance, and whether inflammation, organ injury, and survival are improved after treatment with recombinant human MFG-E8 (rhMFG-E8) after hemorrhagic shock.
METHODS
Male mice underwent a pressure-controlled (25 mm Hg ± 5 mm Hg) model of hemorrhagic shock for 90 minutes. They were resuscitated with normal saline with or without recombinant human MFG-E8 (rhMFG-E8) over 30 minutes. At 3.5-hour postresuscitation, blood and tissue were collected. MFG-E8 levels in the plasma, lungs, and spleen were measured. Apoptotic cell clearance was measured by cleaved caspase-3 levels and TUNEL staining. Neutrophil infiltration was assessed using myeloperoxidase activity in the lungs and spleen. Plasma and tissue levels of proinflammatory cytokines (IL-1β, IL-6, and TNF-α) were measured by ELISA. Finally, a seven-day survival study was also conducted.
RESULTS
MFG-E8 levels in the plasma, lungs, and spleen significantly decreased by 33%, 44%, and 55%, respectively, at 3.5 hour after hemorrhage and resuscitation with rhMFG-E8. Treatment with rhMFG-E8 significantly improved apoptosis, by reducing TUNEL+ cells after treatment and restoring cleaved caspase-3 expression back to baseline. Neutrophil infiltration was blunted by 29% and 41% in the lungs and spleen, respectively. Cytokine expression was also reduced significantly, by 64% to 73% in plasma, 24% to 58% in the lungs, and 49% to 76% in the spleen. Finally, animals demonstrated a superior survival rate over 7 days after treatment with rhMFG-E8.
CONCLUSION
The administration of rhMFG-E8 is a potent treatment in animals after hemorrhagic shock.
背景
凋亡细胞清除不足会导致炎症加剧和器官损伤加重。调理蛋白，乳脂肪球表皮生长因子 8（MFG-E8），上调凋亡细胞清除。本研究旨在确定在失血性休克后接受重组人 MFG-E8（rhMFG-E8）治疗后，凋亡细胞清除的程度，以及炎症、器官损伤和存活率是否得到改善。
方法
雄性小鼠接受压力控制（25 毫米汞柱±5 毫米汞柱）的失血性休克模型 90 分钟。它们用生理盐水复苏，或用生理盐水加重组人 MFG-E8（rhMFG-E8）复苏 30 分钟。在复苏后 3.5 小时，采集血液和组织。测量血浆、肺和脾中的 MFG-E8 水平。通过 cleaved caspase-3 水平和 TUNEL 染色测量凋亡细胞清除。通过肺和脾中的髓过氧化物酶活性评估中性粒细胞浸润。通过 ELISA 测量血浆和组织中的促炎细胞因子（IL-1β、IL-6 和 TNF-α）水平。最后还进行了为期 7 天的生存研究。
结果
rhMFG-E8 治疗显著改善了凋亡，降低了 TUNEL+细胞，恢复了 cleaved caspase-3 的表达。中性粒细胞浸润在肺和脾中分别减少了 29%和 41%。细胞因子表达也显著降低，血浆中降低了 64%至 73%，肺中降低了 24%至 58%，脾中降低了 49%至 76%。最后，rhMFG-E8 治疗的动物在 7 天内的存活率更高。
结论
rhMFG-E8 的给药是失血性休克后动物的一种有效治疗方法。
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