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骨髓间充质干细胞联合辛伐他汀通过激活 Akt/mTOR 通路加速烧伤创面愈合。

Bone Marrow-Derived Mesenchymal Stem Cells Combined With Simvastatin Accelerates Burn Wound Healing by Activation of the Akt/mTOR Pathway.

机构信息

Student Research Committee, Department of Anatomical Sciences, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Department of Anatomical Sciences, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

出版信息

J Burn Care Res. 2020 Sep 23;41(5):1069-1078. doi: 10.1093/jbcr/iraa005.

DOI:10.1093/jbcr/iraa005
PMID:32157277
Abstract

Burn wound healing is one of the most important problems in the field of medical science. Promising results have recently been reported by researchers who used bone marrow mesenchymal stem cells (BMSCs) to treat burn wounds. In this study, we investigated the effects of BMSC therapy in combination with simvastatin (SMV) on angiogenesis as well as on the activity of the Akt/mTOR signaling pathway during burn wound healing in rats. After creating second-degree burn wounds, 40 adult male Wistar rats were randomly divided into four treatment groups: the control, SMV, BMSCs, and the combination therapy group (BMSCs+SMV). Animals were killed 14 days after treatment initiation, and the wounds were removed for histological and molecular analyses. All in all, combination therapy produced better outcomes than individual therapy in terms of the wound closure area, epidermal regeneration level, collagen deposition intensity, and reepithelialization rate. In addition, the elevations of expression levels of Akt and mTOR genes, at both mRNA and protein levels, were more pronounced in the BMSCs+SMV group (P < .05, at least, for both qRT-PCR and western blot assessments). qRT-PCR findings also demonstrated that the wounds treated with the combination of BMSCs and SMV had the highest expression levels of CD31 and VEGF genes (P < .01 for all comparisons). These data suggest that the combined administration of BMSCs transplantation and topical SMV has a great potential in burn wound healing. According to the findings, the beneficial effects of the combination therapy are caused, at least in part, through stimulating Akt/mTOR signaling pathway.

摘要

烧伤创面愈合是医学领域最重要的问题之一。最近,研究人员使用骨髓间充质干细胞(BMSCs)治疗烧伤创面,取得了有希望的结果。在这项研究中,我们研究了 BMSC 治疗联合辛伐他汀(SMV)对大鼠烧伤创面愈合过程中血管生成以及 Akt/mTOR 信号通路活性的影响。在造成二度烧伤创面后,将 40 只成年雄性 Wistar 大鼠随机分为四组治疗:对照组、SMV 组、BMSCs 组和联合治疗组(BMSCs+SMV 组)。在治疗开始后 14 天处死动物,并取出创面进行组织学和分子分析。总的来说,联合治疗在创面闭合面积、表皮再生水平、胶原沉积强度和再上皮化率方面的效果均优于单独治疗。此外,BMSCs+SMV 组 Akt 和 mTOR 基因的表达水平升高更为明显,无论是在 mRNA 还是蛋白水平(P <.05,至少 qRT-PCR 和 Western blot 评估均如此)。qRT-PCR 结果还表明,BMSCs 和 SMV 联合治疗的创面具有最高水平的 CD31 和 VEGF 基因表达(所有比较均 P <.01)。这些数据表明,BMSCs 移植联合局部 SMV 的联合给药在烧伤创面愈合中具有很大的潜力。根据研究结果,联合治疗的有益效果至少部分是通过刺激 Akt/mTOR 信号通路产生的。

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