Bone marrow mesenchymal stem cells alleviate the daunorubicin-induced subacute myocardial injury in rats through inhibiting infiltration of T lymphocytes and antigen-presenting cells
Bone marrow mesenchymal stem cells alleviate the daunorubicin-induced subacute myocardial injury in rats through inhibiting infiltration of T lymphocytes and antigen-presenting cells
复制标题
骨髓间充质干细胞通过抑制T淋巴细胞和抗原呈递细胞浸润减轻柔红霉素诱导的大鼠亚急性心肌损伤
DOI：
10.1016/j.biopha.2019.109157
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发表时间：
2020-01-01
影响因子：
7.5
通讯作者：
Yang，Ting
中科院分区：
文献类型：
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作者：
Chen，Qiuru;Zhang，Yuxin;Yang，Ting
简介从心脏再生治疗的角度对骨髓间充质干细胞（BMSC）进行了广泛的研究。本研究旨在探讨BMSCs对亚急性心肌损伤的保护作用，并确定合适的BMSC回输时间。方法从人骨髓血中分离BMSCs。随后建立柔红霉素（DNR）诱导的亚急性心肌模型。 DNR诱导的亚急性心肌损伤大鼠在不同时间点注射右雷佐生（DZR）和/或BMSC，然后通过评估左心室射血分数（LVEF）和缩短分数（FS）来评估心功能。分析心肌结构变化，检测CD3和人类白细胞抗原DR（HLA-DR）水平，进一步验证BMSCs影响亚急性心肌损伤的机制。结果BMSCs联合DZR治疗可增强DNR诱导的心肌损伤大鼠的心功能，表现为LVEF和FS增加。 BMSCs联合DZR治疗可减轻DNR引起的心肌损伤，并减少浸润或空泡化。此外，观察到 BMSC 可以减轻 T 淋巴细胞和抗原呈递细胞的浸润，CD3 和 HLA-DR 表达减少证明了这一点。 结论 综上所述，本研究表明 BMSC 可以预防 DNR 诱导的心肌损伤，特别是在 DNR 给药的前三天。 BMSCs联合DZR发挥更好的治疗效果，但存在个体差异。
IntroductionBone marrow mesenchymal stem cells (BMSCs) have been extensively investigated from a perspective on cardiac regeneration therapy. The current study aimed to investigate the protective effect conferred by BMSCs in subacute myocardial injury, and to identify an appropriate BMSC reinfusion time.MethodsBMSCs were isolated from human bone marrow blood. Daunorubicin (DNR)-induced subacute myocardial models were subsequently established. The rats with DNR-induced subacute myocardial injury were injected with dexrazoxane (DZR) and/or BMSCs at varying time points, after which cardiac function was evaluated by assessing left ventricular ejection fraction (LVEF) and fraction shortening (FS). The myocardial structural changes were analyzed, after which the levels of CD3 and human leukocyte antigen DR (HLA-DR) were examined to further validate the mechanism by which BMSCs could influence subacute myocardial injury.ResultsBMSCs combined with DZR treatment enhanced the cardiac function of rats with DNR-induced myocardial injury, as reflected by increased LVEF and FS. DNR-induced myocardial injuries were mitigatedviathe application of BMSCs combined with treatment of DZR, accompanied by diminished infiltration or vacuolization. Moreover, BMSCs were observed to alleviate infiltration of T lymphocyte and antigen-presenting cells, as evidenced by reduced expression of CD3 and HLA-DR.ConclusionTaken together, this study demonstrates that BMSCs could protect against DNR-induced myocardial injury, especially in the first three days of DNR administration. BMSCs combined with DZR exert a better therapeutic effect, but there are individual differences.