Potential role of mesenchymal stem cells in alleviating intestinal ischemia/reperfusion impairment.

Potential role of mesenchymal stem cells in alleviating intestinal ischemia/reperfusion impairment.
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DOI:
10.1371/journal.pone.0074468
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Zhu W
Zhu W
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Jiang H;Qu L;Dou R;Lu L;Bian S;Zhu W

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骨髓间充质干细胞(MSCs)的移植为缺血或再灌注损伤引起的各种疾病提供了有希望的治疗效果。我们先前已经证明了MSC在减轻大鼠肠缺血/再灌注(I/R)损伤中的功效,但是MSC移植物改善I/R损伤的机制在很大程度上是未知的。本研究的目的是调查骨髓间充质干细胞发挥其功能的可能机制。雄性供体来源的大鼠MSCs经上级肠系膜动脉夹闭和开放后,直接黏膜下注射植入雌性受体大鼠肠道。采用Y染色体原位杂交探针检测归巢后的MSCs,ELISA法检测肠黏膜中肿瘤坏死因子-α(TNF-α)的含量。实时荧光定量PCR检测肠黏膜增殖细胞核抗原(PCNA)的表达,Western blot检测肠黏膜磷酸化细胞外信号调节激酶(pERK 1/2)和核因子-κB(NF-κB)的表达。MSCs移植后4、7 d,MSCs组肠黏膜TNF-α含量明显低于生理盐水组。骨髓间充质干细胞移植后第4、7天肠黏膜PCNA表达均高于生理盐水组。MSCs移植后4、7 d,MSCs治疗组肠黏膜pERK 1/2表达明显高于生理盐水组,NF-κB表达明显低于生理盐水组。目前的研究提供了新的证据表明,MSC有可能减少肠I/R损伤,可能是由于它们能够加速细胞增殖和减少缺血和再灌注后肠粘膜内的炎症反应。
Transplantation of bone marrow mesenchymal stem cells (MSCs) provides a promising therapeutic efficiency for a variety of disorders caused by ischemia or reperfusion impairment. We have previously demonstrated the efficacy of MSCs in mitigating intestinal ischemia/reperfusion (I/R) injuries in rats, but the mechanism by which MSCs engraft ameliorates I/R injuries has largely been unknown. The present study aimed at investigating probable mechanisms by which MSCs exert their function. Male donor derived rat MSCs were implanted into intestine of female recipient rat by direct submucosal injection after superior mesenteric artery clamping and unclamping. The homed MSCs were detected by Y chromosome in situ hybridization probe, and the tumor necrosis factor-α (TNF-α) content in intestinal mucosa was determined by ELISA. Expression of proliferative cell nuclear antigen (PCNA) in bowel mucosa was assayed by real-time PCR and intestinal mucosa expression of phosphorylation extracellular signal-regulated kinase (pERK1/2) and nuclear factor-κB (NF-κB) were evaluated by western blot. Four and seven days after MSCs transplantation, the TNF-α content of bowel mucosa in MSCs group was significantly lower than that in saline group. The PCNA in bowel mucosa showed higher expression in MSCs treated group than the saline group, both at 4 and 7 days after cell transplantation. The expression of intestinal mucosal pERK1/2 in MSCs treated group was markedly higher than that in saline group, and the expression of NF-κB in MSCs treated group was noticeably decreased than that in saline group at 4 and 7 days post MSCs transplantation. The present investigation provides novel evidence that MSCs have the potential to reduce intestinal I/R injuries probably due to their ability to accelerate cell proliferation and decrease the inflammatory response within intestinal mucosa after ischemia and reperfusion.
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