Abstract：
The goal of this study was to assess the influence of bone marrow-derived mesenchymal stem cells (BM-MSCs) on the nephrotoxicity induced by fractionated doses of gamma irradiation (Rad) and the cotherapy of levetiracetam and oxcarbazepine in male rats. Adult rats were randomly divided into four groups. Group I: Control, Group II: antiepileptic drugs (AEDs), Group III: AEDs +Rad and Group IV: AEDs + Rad + MSCs. Rats treated with AEDs and exposed to fractionated doses of γ-irradiation displayed a discernible increase in serum urea, creatinine, kidney injury marker, kidney malondialdehyde, transforming growth factor beta (TGF-β) and the relative expression of Smad3 along with a decrease in the relative expression of Smad7 and glutathione level. Alternatively, groups treated with BM-MSCs with AEDs and Rad showed a substantial modification in the majority of the evaluated parameters and looked to be successful in reducing the hazards of the combination therapy of AEDs and radiation. The reno-histopathological study supports the biochemical analysis. In conclusion, BM-MSCs exhibited therapeutic potential against nephrotoxicity induced by fractionated doses of γ-irradiation and AEDs. The outcome was brought about by the downregulation of the TGF-β/Smad pathway. BM-MSCs might be suggested as a valuable therapeutic strategy to overcome kidney injury induced by gamma irradiation during AEDs cotherapy.
摘要：
这项研究的目的是评估骨髓间充质干细胞（BM-MSCs）对雄性大鼠中分级剂量的γ辐射（Rad）和左乙拉西坦和奥卡西平的联合治疗引起的肾毒性的影响。成年年夜鼠随机分为四组。第一组:控制,第二组：抗癫痫药（AEDs），组III:AED+Rad和组IV:AED+Rad+MSC。用AED治疗并暴露于分级剂量的γ辐射的大鼠显示出血清尿素的明显增加，肌酐,肾损伤标志物，肾脏丙二醛，转化生长因子β（TGF-β）和Smad3的相对表达随着Smad7和谷胱甘肽水平的相对表达降低。或者，用AED和Rad的BM-MSCs治疗的组显示出大多数评估参数的实质性改变,并且看起来在降低AED和放射联合治疗的危害方面是成功的。肾组织病理学研究支持生化分析。总之,BM-MSC表现出针对分级剂量的γ-辐射和AED诱导的肾毒性的治疗潜力。该结果由TGF-β/Smad途径的下调引起。BM-MSCs可能被认为是一种有价值的治疗策略，可以克服AEDs联合治疗期间γ辐射引起的肾损伤。
