Targeting the gut to prevent sepsis from a cutaneous burn
Targeting the gut to prevent sepsis from a cutaneous burn
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DOI：
10.1172/jci.insight.137128
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发表时间：
2020-10-02
期刊：
影响因子：
8
通讯作者：
Hodin, Richard A.
中科院分区：
文献类型：
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作者：
Adiliaghdam, Fatemeh;Cavallaro, Paul;Hodin, Richard A.
严重的烧伤会引起肠道屏障功能障碍，随后会引起严重的全身炎症反应。在本研究中，我们研究了小肠刷边酶肠碱性磷酸酶（lAP）在小鼠烧伤创面感染后维持肠道屏障功能和预防全身炎症的作用。在皮下注射或不注射铜绿假单胞菌的情况下，对小鼠进行30%体表面积的背部烧伤。小鼠在损伤后3、12小时分别灌胃2000单位lAP或载药。我们发现，在这个烧伤感染模型中，内源性和外源性补充lAP都能显著减少肠道屏障损伤，减少细菌向全身器官的易位，减轻全身炎症，提高生存率。IAP可减轻肝脏炎症，降低门静脉血清的促炎特性。此外，我们发现，与对照组小鼠相比，烧伤创面感染小鼠的肠内腔内容物对肠上皮完整性有负面影响，而补充IAP可以保持单层完整性。这些结果表明，口服IAP治疗可能是一种保护肠道屏障功能、阻止促炎触发物进入门静脉系统、预防肠道诱导的全身性炎症和提高严重烧伤后生存率的方法。
Severe burn injury induces gut barrier dysfunction and subsequently a profound systemic inflammatory response. In the present study, we examined the role of the small intestinal brush border enzyme, intestinal alkaline phosphatase (lAP), in preserving gut barrier function and preventing systemic inflammation after burn wound infection in mice. Mice were subjected to a 30% total body surface area dorsal burn with or without intradermal injection of Pseudomonas ceruginosa. Mice were gavaged with 2000 units of lAP or vehicle at 3 and 12 hours after the insult. We found that both endogenously produced and exogenously supplemented lAP significantly reduced gut barrier damage, decreased bacterial translocation to the systemic organs, attenuated systemic inflammation, and improved survival in this burn wound infection model. IAP attenuated liver inflammation and reduced the proinflammatory characteristics of portal serum. Furthermore, we found that intestinal luminal contents of burn wound-infected mice negatively impacted the intestinal epithelial integrity compared with luminal contents of control mice and that IAP supplementation preserved monolayer integrity. These results indicate that oral IAP therapy may represent an approach to preserving gut barrier function, blocking proinflammatory triggers from entering the portal system, preventing gut-induced systemic inflammation, and improving survival after severe burn injuries.