The influence of intestinal ischemia and reperfusion on bidirectional intestinal barrier permeability, cellular membrane integrity, proteinase inhibitors, and cell death in rats

The influence of intestinal ischemia and reperfusion on bidirectional intestinal barrier permeability, cellular membrane integrity, proteinase inhibitors, and cell death in rats
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DOI:
10.1097/00024382-199809000-00009
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发表时间:
1998-09-01
期刊:
影响因子:
3.1
通讯作者:
Andersson, R
Andersson, R
中科院分区:
医学2区
文献类型:
--
作者:
Sun, ZW;Wang, XD;Andersson, R

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肠缺血再灌注损伤(I/R)可能参与肠屏障功能障碍的发病机制,与肠道细菌和毒素的易位相关,并可能发展为多器官功能衰竭。肠道内皮和上皮层在阻止有毒物质进入肠道中发挥着重要作用,但蛋白酶-抗蛋白酶系统平衡对这些屏障功能的影响以及上皮DNA合成、细胞凋亡和内皮和上皮屏障大分子通透性之间的关系尚未得到充分研究。在大鼠肠缺血20和40 min,再灌注1、3、6、12 h时,测量内皮和上皮屏障大分子通透性、上皮DNA合成、内皮和上皮质膜系统、细胞凋亡和肿瘤、血浆蛋白酶抑制剂和前酶水平。内皮通透性在肠缺血20和40 min后均升高,上皮通透性在缺血20 min后1-6 h再灌注和缺血40 min后1-12 h再灌注期间显著升高。缺血20 min再灌注12 h后,上皮细胞DNA合成增加。再灌注3小时后,缺血20分钟和40分钟后,血浆中预钾化钾素、c1酯酶抑制剂和α - 1巨球蛋白水平均显著降低。缺血20 min再灌注12 h后,上皮细胞凋亡显著增加。肠内皮和上皮屏障再灌注损伤的严重程度似乎与缺血时间、细胞损伤和死亡途径以及蛋白酶-抗蛋白酶失衡有关。
Intestinal ischemia and reperfusion injury (I/R) is probably involved in the pathogenesis of intestinal barrier dysfunction, associated with the concomitant translocation of enteric bacteria and toxins and the potential development of multiple organ failure. The intestinal endothelial and epithelial layers play a major role preventing the entry of toxic substances from the gut, but the influence of protease-antiprotease systemic balance on these barrier functions and the relationship between epithelial DNA synthesis, apoptosis, and endothelial and epithelial barrier macromolecule permeability are not fully investigated. Endothelial and epithelial barrier macromolecular permeability, epithelial DNA synthesis, the endothelial and epithelial plasma membrane system, apoptosis and oncosis, plasma levels of proteinase inhibitors, and proenzymes were measured in rats subjected to 20 and 40 min intestinal ischemia and 1, 3, 6, or 12 h reperfusion. Endothelial permeability increased after both 20 and 40 min intestinal ischemia, Epithelial permeability significantly increased during 1-6 h reperfusion after 20 min ischemia and during 1-12 h reperfusion after 40 min ischemia. Epithelial DNA synthesis increased in animals with 20 min ischemia followed by 12 h reperfusion. Plasma levels of prekallikrein, C1-esterase inhibitor, and alpha 1-macroglobulin were significantly lower following both 20 and 40 min ischemia from 3 h reperfusion and on. Apoptotic epithelial cells significantly increased in animals subjected to 20 min ischemia followed by 12 h reperfusion. The severity of reperfusion injury in the intestinal endothelial and epithelial barrier seems to correlate with the period of ischemia and the pathway of cell damage and death, together with proteinase-antiproteinase imbalance.