Bone-marrow mesenchymal stem cells reduce rat intestinal ischemia-reperfusion injury, ZO-1 downregulation and tight junction disruption via a TNF-α-regulated mechanism
Bone-marrow mesenchymal stem cells reduce rat intestinal ischemia-reperfusion injury, ZO-1 downregulation and tight junction disruption via a TNF-α-regulated mechanism
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DOI：
10.3748/wjg.v19.i23.3583
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发表时间：
2013-06-21
影响因子：
4.3
通讯作者：
Zheng, Wei-Ping
中科院分区：
文献类型：
--
作者：
Shen, Zhong-Yang;Zhang, Jing;Zheng, Wei-Ping
目的：探讨骨髓间充质干细胞(BM MSCs)在缺血再灌注(I/R)损伤中对肠粘膜屏障的影响。方法：采用密度梯度离心法分离、培养大鼠骨髓间充质干细胞(BM MSCs)，并进行流式细胞仪分析。结扎肠系膜上动脉30min造成I/R损伤。大鼠接受生理盐水、骨髓间充质干细胞(通过黏膜内注射)或肿瘤坏死因子-α阻断抗体(经尾静脉)治疗。结果：I/R后肠通透性增加，紧密连接(TJ)被破坏，闭塞带1区(ZO-1)表达下调。骨髓间充质干细胞减少肠粘膜屏障破坏、ZO-1下调和TJ破坏。肠I/R损伤后的形态学改变与血清肿瘤坏死因子-α水平呈正相关。给予抗肿瘤坏死因子-αIg G或抗肿瘤坏死因子-α受体1抗体可减轻肠道超微结构改变、ZO-1表达下调和TJ损伤。结论：血清中肿瘤坏死因子-α水平的改变在骨髓间充质干细胞抵抗肠道I/R损伤的能力中起重要作用。(C)2013年白石登。版权所有。
AIM: To investigate the effect of bone-marrow mesenchymal stem cells (BM MSCs) on the intestinal mucosa barrier in ischemia/reperfusion (I/R) injury.METHODS: BM MSCs were isolated from male Sprague-Dawley rats by density gradient centrifugation, cultured, and analyzed by flow cytometry. I/R injury was induced by occlusion of the superior mesenteric artery for 30 min. Rats were treated with saline, BM MSCs (via intramucosal injection) or tumor necrosis factor (TNF)-alpha blocking antibodies (via the tail vein). I/R injury was assessed using transmission electron microscopy, hematoxylin and eosin (HE) staining, immunohistochemistry, western blotting and enzyme linked immunosorbent assay.RESULTS: Intestinal permeability increased, tight junctions (TJs) were disrupted, and zona occludens 1 (ZO-1) was downregulated after I/R injury. BM MSCs reduced intestinal mucosal barrier destruction, ZO-1 downregulation, and TJ disruption. The morphological abnormalities after intestinal I/R injury positively correlated with serum TNF-alpha levels. Administration of anti-TNF-alpha IgG or anti-TNF-alpha receptor 1 antibodies attenuated the intestinal ultrastructural changes, ZO-1 downregulation, and TJ disruption.CONCLUSION: Altered serum TNF-alpha levels play an important role in the ability of BM MSCs to protect against intestinal I/R injury. (c) 2013 Baishideng. All rights reserved.