Bone marrow mesenchymal stem cell transplantation improves radiation-induced heart injury through DNA damage repair in rat model
Bone marrow mesenchymal stem cell transplantation improves radiation-induced heart injury through DNA damage repair in rat model
复制标题
骨髓间充质干细胞移植通过修复大鼠模型中的DNA损伤改善辐射引起的心脏损伤
DOI：
10.1007/s00411-016-0675-0
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发表时间：
2017-03-01
影响因子：
1.7
通讯作者：
Yuan, Zhengwei
中科院分区：
文献类型：
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作者：
Gao, Song;Zhao, Zhiying;Yuan, Zhengwei
放射治疗是治疗大多数胸部恶性肿瘤的有效方法。然而，高剂量辐射引起的心肌损伤是一种严重的并发症。本研究旨在研究间充质干细胞（MSC）移植减轻辐射引起的心肌损伤的可能性。我们将骨髓中提取的骨髓间充质干细胞（BMSCs）经尾静脉移植到辐射性心脏损伤（RIHI）大鼠模型中。将大鼠分为6组：Sham组、IRR（辐照）组和4个不同时间点的IRR + BMSCs移植组。照射后，骨髓间充质干细胞移植可显著增强大鼠心功能。通过分析PPAR-α、PPAR-γ、TGF-β、IL-6和il -8的表达，我们发现BMSC移植减轻了辐射性心肌纤维化，减轻了炎症反应。此外，我们发现，与IRR组相比，IRR + BMSCs移植组大鼠心肌中与DNA修复相关的γ- h2ax、XRCC4、DNA ligase4和tp53bp1的表达上调，生长因子ssdf -1、CXCR4、VEGF和igfin的分泌增加。因此，骨髓间充质干细胞移植有可能通过DNA修复改善RIHI，成为心肌损伤患者的一种新的治疗方法。
Radiotherapy is an effective form of therapy for most thoracic malignant tumors. However, myocardial injury resulting from the high doses of radiation is a severe complication. Here we aimed to study the possibility of reducing radiation-induced myocardial injury with mesenchymal stem cell (MSC) transplantation. We used MSCs extracted from bone marrow (BMSCs) to transplant via the tail vein into a radiation-induced heart injury (RIHI) rat model. The rats were divided into six groups: a Sham group, an IRR (irradiation) group, and four IRR + BMSCs transplantation groups obtained at different time points. After irradiation, BMSC transplantation significantly enhanced the cardiac function in rats. By analyzing the expression ofPPAR-α,PPAR-γ,TGF-β,IL-6, andIL-8, we found that BMSC transplantation alleviated radiation-induced myocardial fibrosis and decreased the inflammatory reaction. Furthermore, we found that expression ofγ-H2AX,XRCC4,DNA ligase4, andTP53BP1, which are associated with DNA repair, was up-regulated, along with increased secretion of growth factorsSDF-1,CXCR4,VEGF, andIGFin rat myocardium in the IRR + BMSCs transplantation groups compared with the IRR group. Thus, BMSC transplantation has the potential to improve RIHI via DNA repair and be a new therapeutic approach for patients with myocardial injury.