A Soliman Nabil, Abd-Allah Somia H, Hussein Samia, Alaa Eldeen Muhammad
Zoology Department, Physiology Section, Faculty of Science, Zagazig University, Egypt.
Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Zagazig University, Egypt.
IUBMB Life. 2017 Mar;69(3):162-169. doi: 10.1002/iub.1600. Epub 2017 Jan 12.
Doxorubicin is an effective anti-neoplastic drug but its use is limited by its cardiotoxicity. Administration of mesenchymal stem cells (MSCs) for the management of cardiotoxicity was with poor myocardial homing capacity. With the aim of developing novel techniques to improve the migration of MSCs, we tested whether valproate and electric fields (EFs) direct the migration of MSCs towards the damaged myocardium. The study included five groups of female albino rats. The first group included 10 healthy rats as normal control group. The remaining 40 female rats received doxorubicin for induction of acute cardiotoxicity. Four rats were sacrificed for histopathological confirmation of cardiotoxicity. The remaining rats were equally divided into subsequent four groups. The second group included nine rats that did not receive further treatment (positive control group). The third group included nine rats which received intravenous bone marrow derived mesenchymal stem cells (BM-MSCs) after cardiotoxicity induction. The fourth group included nine rats which received BM-MSCs plus sodium valporate after cardiotoxicity induction. The fifth group included nine rats which received BM-MSCs plus sodium valporate after cardiotoxicity induction and were exposed to an electrical stimulation (ES). Blood samples were taken from all groups at the end of the study to estimate creatine kinase-MB (CK-MB), aspartate transaminase (AST) and lactate dehydrogenase (LDH). Heart tissues from all rats were used for RNA extraction for assessment of sry gene expression. Homing was tested by PKH26 fluorescence in myocardial tissue sections and by sry gene expression. The best biochemical and histopathological improvement in cardiotoxicity was demonstrated in group 5 (rats that received ES and valporate with MSCs). We concluded that EFs and sodium valproate enhance homing ability of MSCs towards the damaged myocardium in doxorubicin induced carditoxicity model. © 2017 IUBMB Life, 69(3):162-169, 2017.
阿霉素是一种有效的抗肿瘤药物，但其使用因心脏毒性而受到限制。间充质干细胞（MSCs）用于治疗心脏毒性时，其心肌归巢能力较差。为了开发新技术以改善MSCs的迁移，我们测试了丙戊酸盐和电场（EFs）是否能引导MSCs向受损心肌迁移。该研究包括五组雌性白化大鼠。第一组包括10只健康大鼠作为正常对照组。其余40只雌性大鼠接受阿霉素以诱导急性心脏毒性。处死4只大鼠进行心脏毒性的组织病理学确认。其余大鼠平均分为后续四组。第二组包括9只未接受进一步治疗的大鼠（阳性对照组）。第三组包括9只在诱导心脏毒性后接受静脉注射骨髓来源间充质干细胞（BM-MSCs）的大鼠。第四组包括9只在诱导心脏毒性后接受BM-MSCs加丙戊酸钠的大鼠。第五组包括9只在诱导心脏毒性后接受BM-MSCs加丙戊酸钠并接受电刺激（ES）的大鼠。在研究结束时从所有组采集血样以估计肌酸激酶-MB（CK-MB）、天冬氨酸转氨酶（AST）和乳酸脱氢酶（LDH）。所有大鼠的心脏组织用于RNA提取以评估sry基因表达。通过心肌组织切片中的PKH26荧光和sry基因表达测试归巢情况。第5组（接受ES和丙戊酸盐与MSCs的大鼠）在心脏毒性方面表现出最佳的生化和组织病理学改善。我们得出结论，在阿霉素诱导的心脏毒性模型中，EFs和丙戊酸钠可增强MSCs向受损心肌的归巢能力。©2017国际生物化学与分子生物学联盟生命科学，69(3):162 - 169，2017。
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