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α-Lipoic acid and amlodipine/perindopril combination potentiate the therapeutic effect of mesenchymal stem cells on isoproterenol induced cardiac injury in rats
Biochimie ( IF 3.9 ) Pub Date : 2018-10-08 , DOI: 10.1016/j.biochi.2018.10.002
Abeer I. Abd El-Fattah , M.S. Zaghloul , N.A. Eltablawy , L.A. Rashed

Cardiac injury is a dangerous disease and become a greater issue in the forthcoming decades. The ultimate goal is to prevent the progression of heart failure and apoptotic processes. Cardiac tissue may regenerate itself but to certain extent depending on the number of resident stem cells that is limited. Thus, research had been focused on bone marrow derived stem cells (BM-MSCs) as a promising therapy in different types of tissues, including the heart. This study is designed not only to assess the therapeutic effect of BM-MSCs but also to improve their therapeutic effect in combination with antioxidant α-lipoic acid (ALA) and antihypertensive therapeutic drug form (AP) against isoproterenol-induced cardiac injury and compared with that of BM-MSCs alone. Cardiac injury was induced in 70 male rats by Isoproterenol (ISO was injected s.c. for four consecutive days). Experimental animals were divided into six ISO-treated groups beside a control non treated one. The six ISO-treated groups were divided into: ISO group, ISO+BM-MSCs group, ISO+ALA group, ISO+AP group, ISO+ALA+AP group and ISO+ALA+AP+BM-MSCs group, the last five groups were treated with the examined materials after one week of ISO injection. Isoproterenol significantly increased serum CK-MB, LDH activities, Troponin1 and TNF-α. Oxidative stress is evidenced by the increased MDA, NO and Caspase-3 activity associated with significant reduction of GSH content and SOD activity in cardiac tissue. Furthermore, mRNA expression of NFκB and iNOS were significantly up regulated and eNOS mRNA expression was down regulated. Administration of BM-MSCs, ALA and AP alone significantly mitigated the induced cardiac injury. Concomitant administration of ALA and AP after BM-MSCs induced a more pronounced improving effect on cardiac functions. In conclusion, the concomitant administration of ALA and AP after BM-MSCs infusion increases the cellular antioxidant levels of cardiac tissue that improves the repairing function of BM-MSCs.



中文翻译:

α-硫辛酸和氨氯地平/培哚普利组合可增强间充质干细胞对异丙肾上腺素所致大鼠心脏的治疗作用

心脏损伤是一种危险的疾病,在接下来的几十年中将成为一个更大的问题。最终目标是防止心力衰竭和凋亡过程的发展。心脏组织可能会自身再生,但在一定程度上取决于有限的驻留干细胞的数量。因此,研究集中在骨髓衍生干细胞(BM-MSC),作为在包括心脏在内的不同类型组织中的一种有前途的疗法。这项研究不仅旨在评估BM-MSC的治疗效果,而且还与抗氧化剂α-硫辛酸(ALA)和抗高血压治疗药物形式(AP)联合治疗对异丙肾上腺素引起的心脏损伤的效果进行了比较,并与仅是BM-MSC的。异丙肾上腺素诱发70只雄性大鼠心脏损伤(皮下注射ISO 连续四天)。除了未处理的对照组外,将实验动物分为六个经ISO处理的组。六个ISO治疗组分为:ISO组,ISO + BM-MSCs组,ISO + ALA组,ISO + AP组,ISO + ALA + AP组和ISO + ALA + AP + BM-MSCs组,最后一组ISO注射一周后,对五组患者进行了检查。异丙肾上腺素显着增加血清CK-MB,LDH活性,肌钙蛋白1和TNF-α。MDA,NO和Caspase-3活性的增加与心脏组织中GSH含量和SOD活性的显着降低有关,证明了氧化应激。此外,NFκB和iNOS的mRNA表达显着上调,而eNOS mRNA的表达下调。单独施用BM-MSC,ALA和AP可显着减轻诱发的心脏损伤。BM-MSCs后同时给予ALA和AP可以改善心脏功能。总之,在输注BM-MSC后,同时使用ALA和AP可增加心脏组织的细胞抗氧化水平,从而改善BM-MSC的修复功能。

更新日期:2018-10-08
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