Mesenchymal Stem Cells Ameliorate Hepatic Ischemia/Reperfusion Injury via Inhibition of Neutrophil Recruitment
Mesenchymal Stem Cells Ameliorate Hepatic Ischemia/Reperfusion Injury via Inhibition of Neutrophil Recruitment
复制标题
间充质干细胞通过抑制中性粒细胞募集改善肝脏缺血/再灌注损伤
DOI：
10.1155/2018/7283703
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发表时间：
2018-01-01
影响因子：
4.1
通讯作者：
Yang, Yang
中科院分区：
文献类型：
--
作者：
Li, Shihui;Zheng, Xu;Yang, Yang
缺血/再灌注损伤（Ischemia/reperfusion injury，IRI）是器官移植术后移植物功能障碍的主要原因。肝脏IRI的特征在于肝脏内的过度炎症反应。间充质干细胞（MSCs）是一种免疫调节细胞，对多种器官的IRI具有治疗作用。然而，MSC对IRI的调节作用机制尚不清楚。在本研究中，我们研究了骨髓间充质干细胞对肝脏炎症反应的影响，如中性粒细胞流入和肝脏损伤的大鼠模型中的70%肝IRI。骨髓间充质干细胞治疗可显著降低大鼠肝脏IRI的血清肝酶水平，减轻肝脏中性粒细胞浸润，减少肝硬化相关蛋白的表达，减轻肝脏病理损伤。MSC还显著增强了细胞内p38 MAPK磷酸化的激活，这导致中性粒细胞表面CXCR 2的表达降低。此外，MSC通过抑制巨噬细胞中的NF-B p65磷酸化显著减少中性粒细胞趋化因子CXCL 2的产生。这些结果表明，MSC显著改善肝脏IRI主要是通过其对肝脏中性粒细胞迁移和浸润的抑制作用。
Ischemia/reperfusion injury (IRI) remains a major problem in organ transplantation, which represents the main cause of graft dysfunction posttransplantation. Hepatic IRI is characterized by an excessive inflammatory response within the liver. Mesenchymal stem cells (MSCs) have been shown to be immunomodulatory cells and have the therapeutic action on IRI in several organs. However, the mechanism of regulatory effect of MSCs on IRI remains unclear. In the present study, we examined the impact of MSCs on hepatic inflammatory response such as neutrophil influx and liver damage in a rat model of 70% hepatic IRI. Treatment with MSCs protected rat against hepatic IRI, with significantly decreased serum levels of liver enzymes, attenuated hepatic neutrophil infiltration, reduced expression of apoptosis-associated proteins, and ameliorated liver pathological injury. MSCs also significantly enhanced the intracellular activation of p38 MAPK phosphorylation, which led to decreased expression of CXCR2 on the surface of neutrophils. In addition, MSCs significantly diminished neutrophil chemoattractant CXCL2 production by inhibiting NF-B p65 phosphorylation in macrophages. These results demonstrate that MSCs significantly ameliorate hepatic IRI predominantly through its inhibitory effect on hepatic neutrophil migration and infiltration.