Transmural intestinal wall permeability in severe ischemia after enteral protease inhibition.
Transmural intestinal wall permeability in severe ischemia after enteral protease inhibition.
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DOI：
10.1371/journal.pone.0096655
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Penn AH
中科院分区：
文献类型：
--
作者：
Altshuler AE;Lamadrid I;Li D;Ma SR;Kurre L;Schmid-Schönbein GW;Penn AH
在肠缺血中，小肠腔中的炎性介质如食物副产物、细菌和消化酶渗漏到腹膜空间、淋巴和循环中，但是肠壁通透性最初增加的机制还没有很好地定义。我们假设肠壁蛋白酶活性（独立于腔蛋白酶）和细胞凋亡导致急性缺血小肠肠壁透壁性增加。为了建立肠缺血模型，切除大鼠的近端空肠至远端回肠，用盐水快速冲洗管腔以除去管腔内容物，切成等长的段，并填充盐水、葡萄糖或蛋白酶抑制剂中的示踪剂（荧光素）。在2小时内测定透壁荧光素转运。绒毛结构和上皮连接蛋白进行了分析。缺血后，跨壁渗透性增加，绒毛结构丧失，上皮蛋白质破坏。补充鲁米那葡萄糖保存上皮细胞和显着衰减的渗透性和绒毛损伤。基质金属蛋白酶（MMP）抑制剂（强力霉素，GM 6001），丝氨酸蛋白酶抑制剂（氨甲环酸）在管腔中，显着减少荧光素运输相比，盐水缺血90分钟。基于这些结果，我们在失血性休克的体内模型（90分钟30 mmHg，3小时观察）中测试肠损伤形成。单一肠内干预（生理盐水，葡萄糖，氨甲环酸）不能防止肠道病变，而肠内葡萄糖和氨甲环酸的组合防止出血性休克后病变的形成。结果表明，细胞凋亡和蛋白酶介导的分解导致肠壁通透性增加和损伤。在缺血肠的管腔中用葡萄糖进行代谢支持减少了从管腔穿过肠壁的转运，并且肠内蛋白水解抑制减弱了组织分解。这些联合干预措施改善了出血性休克后小肠的病变形成。
In intestinal ischemia, inflammatory mediators in the small intestine's lumen such as food byproducts, bacteria, and digestive enzymes leak into the peritoneal space, lymph, and circulation, but the mechanisms by which the intestinal wall permeability initially increases are not well defined. We hypothesize that wall protease activity (independent of luminal proteases) and apoptosis contribute to the increased transmural permeability of the intestine's wall in an acutely ischemic small intestine. To model intestinal ischemia, the proximal jejunum to the distal ileum in the rat was excised, the lumen was rapidly flushed with saline to remove luminal contents, sectioned into equal length segments, and filled with a tracer (fluorescein) in saline, glucose, or protease inhibitors. The transmural fluorescein transport was determined over 2 hours. Villi structure and epithelial junctional proteins were analyzed. After ischemia, there was increased transmural permeability, loss of villi structure, and destruction of epithelial proteins. Supplementation with luminal glucose preserved the epithelium and significantly attenuated permeability and villi damage. Matrix metalloproteinase (MMP) inhibitors (doxycycline, GM 6001), and serine protease inhibitor (tranexamic acid) in the lumen, significantly reduced the fluorescein transport compared to saline for 90 min of ischemia. Based on these results, we tested in an in-vivo model of hemorrhagic shock (90 min 30 mmHg, 3 hours observation) for intestinal lesion formation. Single enteral interventions (saline, glucose, tranexamic acid) did not prevent intestinal lesions, while the combination of enteral glucose and tranexamic acid prevented lesion formation after hemorrhagic shock. The results suggest that apoptotic and protease mediated breakdown cause increased permeability and damage to the intestinal wall. Metabolic support in the lumen of an ischemic intestine with glucose reduces the transport from the lumen across the wall and enteral proteolytic inhibition attenuates tissue breakdown. These combined interventions ameliorate lesion formation in the small intestine after hemorrhagic shock.
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人类肠道缺血再灌注的快速逆转通过脱落受伤的肠上皮细胞和再上皮化引起的损害。
影响因子：
3.7
作者：
Derikx, Joep P. M.;Matthijsen, Robert A.;de Bruine, Adriaan P.;van Bijnen, Annemarie A.;Heineman, Erik;van Dam, Ronald M.;Dejong, Cornelis H. C.;Buurman, Wim A.
通讯作者：
Buurman, Wim A.
DOI：
10.1111/j.1749-6632.2010.05713.x
发表时间：
2010-01-01
期刊：
LYMPHATICS IN THE DIGESTIVE SYSTEM: PHYSIOLOGY, HEALTH, AND DISEASE
影响因子：
--
作者：
Deitch, Edwin A.
通讯作者：
Deitch, Edwin A.
影响因子：
24.5
作者：
HAGLUND, U
通讯作者：
HAGLUND, U
影响因子：
3.7
作者：
Chang M;Alsaigh T;Kistler EB;Schmid-Schönbein GW
通讯作者：
Schmid-Schönbein GW
影响因子：
5.8
作者：
Hu, JL;Van den Steen, PE;Opdenakker, G
通讯作者：
Opdenakker, G