Fishman Jordan E, Sheth Sharvil U, Levy Gal, Alli Vamsi, Lu Qu, Xu Dazhong, Qin Yung, Qin Xiaofa, Deitch Edwin A
From the Department of Surgery, UMDNJ-NJMS, Newark, NJ.
Ann Surg. 2014 Dec;260(6):1112-20. doi: 10.1097/SLA.0000000000000631.
To test whether the mucus layer, luminal digestive enzymes, and intestinal mast cells are critical components in the pathogenesis of trauma shock-induced gut and lung injury.
Gut origin sepsis studies have highlighted the importance of the systemic component (ischemia-reperfusion) of gut injury, whereas the intraluminal component is less well studied.
In rats subjected to trauma hemorrhagic shock (T/HS) or sham shock, the role of pancreatic enzymes in gut injury was tested by diversion of pancreatic enzymes via pancreatic duct exteriorization whereas the role of the mucus layer was tested via the enteral administration of a mucus surrogate. In addition, the role of mast cells was assessed by measuring mast cell activation and the ability of pharmacologic inhibition of mast cells to abrogate gut and lung injury. Gut and mucus injury was characterized functionally, morphologically, and chemically.
Pancreatic duct exteriorization abrogated T/HS-induced gut barrier loss and limited chemical mucus changes. The mucus surrogate prevented T/HS-induced gut and lung injury. Finally, pancreatic enzyme-induced gut and lung injury seems to involve mast cell activation because T/HS activates mast cells and pharmacologic inhibition of intestinal mast cells prevented T/HS-induced gut and lung injury.
These results indicate that gut and gut-induced lung injury after T/HS involves a complex process consisting of intraluminal digestive enzymes, the unstirred mucus layer, and a systemic ischemic-reperfusion injury. This suggests the possibility of intraluminal therapeutic strategies.
测试黏液层、腔内消化酶和肠道肥大细胞是否为创伤性休克诱导的肠道和肺损伤发病机制中的关键组成部分。
肠道源性脓毒症研究突出了肠道损伤的全身组成部分(缺血再灌注)的重要性,而腔内组成部分的研究较少。
在遭受创伤性失血性休克(T/HS)或假休克的大鼠中,通过胰管外置引流胰酶来测试胰酶在肠道损伤中的作用,而通过肠内给予黏液替代物来测试黏液层的作用。此外,通过测量肥大细胞活化以及药物抑制肥大细胞消除肠道和肺损伤的能力来评估肥大细胞的作用。从功能、形态和化学方面对肠道和黏液损伤进行表征。
胰管外置可消除T/HS诱导的肠道屏障丧失并限制化学性黏液变化。黏液替代物可预防T/HS诱导的肠道和肺损伤。最后,胰酶诱导的肠道和肺损伤似乎涉及肥大细胞活化,因为T/HS可激活肥大细胞,而药物抑制肠道肥大细胞可预防T/HS诱导的肠道和肺损伤。
这些结果表明,T/HS后肠道及肠道诱导的肺损伤涉及一个复杂的过程,该过程由腔内消化酶、静止的黏液层和全身性缺血再灌注损伤组成。这提示了腔内治疗策略的可能性。