Inan M, Bakar E, Cerkezkayabekir A, Sanal F, Ulucam E, Subaşı C, Karaöz E
Department of Pediatric Surgery, Trakya University Faculty of Medicine, Edirne, Turkey.
Department of Pharmaceutical Technology, Trakya University Faculty of Pharmacy, Edirne, Turkey.
J Pediatr Surg. 2017 Jul;52(7):1196-1206. doi: 10.1016/j.jpedsurg.2016.12.024. Epub 2017 Jan 2.
Mesenchymal stem cells (MSCs) may have beneficial effects in reversing intestinal damage resulting from circulatory disorders. The hypothesis of this study is that MSCs increase antioxidant capacity of small bowel tissue following intestinal ischemia reperfusion (I/R) damage.
A total of 100 rats were used for the control group and three experimental groups, as follows: the sham control, local MSC, and systemic MSC groups. Each group consisted of 10 animals on days 1, 4, and 7 of the experiment. Ischemia was established by clamping the superior mesenteric artery (SMA) for 45min; following this, reperfusion was carried out for 1, 4, and 7days in all groups. In the local and systemic groups, MSCs were administered intravenously and locally just after the ischemia, and they were investigated after 1, 4, and 7days. The superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (Gpx) activities, as well as malondialdehyde (MDA) and total protein levels, were measured. Histopathological analysis was performed using light and electron microscopy. The indicators of proliferation from the effects of anti- and pro-inflammatory cytokines were evaluated using immunohistochemistry.
MDA was increased (P<0.05) in the sham control group and decreased (P<0.05) in the MSC groups. SOD, CAT, and Gpx were decreased in the local MSC group (P<0.05). The highest level of amelioration was observed on day 7 in the local MSC group via light and electron microscopy. It was found that the MSCs arrived at the damaged intestinal wall in the MSC groups immediately after injection. Pro-inflammatory cytokines interleukin-1β (IL1β), transforming growth factor-β1 (TGFβ1), tumor necrosis factor-α (TNFα), IL6, MIP2, and MPO decreased (P<0.05), while anti-inflammatory cytokines EP3 and IL1ra increased (p<0.05) in the local and systemic MSC groups. In addition, proliferation indicators, such as PCNA and KI67, increased (P<0.05) in the local and systemic MSC groups.
Parallel to our hypothesis, MSC increases the antioxidant capacity of small bowel tissue after intestinal I/R damage. The MSCs migrated to the reperfused small intestine by homing and reduced oxidative stress via the effects of SOD, CAT, and Gpx, as well as reducing the MDA level; thus, they could increase antioxidant capacity of intestine and have a therapeutic effect on the damaged tissue. We think that this effect was achieved via scavenging of oxygen radicals, suppression of pro-inflammatory cytokines, and increasing the expression of anti-inflammatory cytokines.
间充质干细胞（MSCs）可能对逆转循环障碍导致的肠道损伤具有有益作用。本研究的假设是，间充质干细胞可增加肠道缺血再灌注（I/R）损伤后小肠组织的抗氧化能力。
总共100只大鼠被用于对照组和三个实验组，具体如下：假手术对照组、局部间充质干细胞组和全身间充质干细胞组。在实验的第1天、第4天和第7天，每组由10只动物组成。通过夹闭肠系膜上动脉（SMA）45分钟建立缺血模型；之后，所有组均进行1天、4天和7天的再灌注。在局部和全身组中，缺血后立即静脉内和局部给予间充质干细胞，并在1天、4天和7天后进行研究。测量超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和谷胱甘肽过氧化物酶（Gpx）活性，以及丙二醛（MDA）和总蛋白水平。使用光镜和电镜进行组织病理学分析。使用免疫组织化学评估抗炎和促炎细胞因子作用下的增殖指标。
假手术对照组中MDA增加（P<0.05），间充质干细胞组中MDA减少（P<0.05）。局部间充质干细胞组中SOD、CAT和Gpx减少（P<0.05）。通过光镜和电镜观察，局部间充质干细胞组在第7天观察到最高程度的改善。发现间充质干细胞组注射后立即到达受损肠壁。局部和全身间充质干细胞组中促炎细胞因子白细胞介素-1β（IL1β）、转化生长因子-β1（TGFβ1）、肿瘤坏死因子-α（TNFα）、IL6、MIP2和MPO减少（P<0.05），而抗炎细胞因子EP3和IL1ra增加（P<0.05）。此外，局部和全身间充质干细胞组中增殖指标，如增殖细胞核抗原（PCNA）和Ki67增加（P<0.05）。
与我们的假设一致，间充质干细胞增加肠道I/R损伤后小肠组织的抗氧化能力。间充质干细胞通过归巢迁移至再灌注的小肠，并通过SOD、CAT和Gpx的作用降低氧化应激，同时降低MDA水平；因此，它们可增加肠道的抗氧化能力，并对受损组织具有治疗作用。我们认为这种作用是通过清除氧自由基、抑制促炎细胞因子和增加抗炎细胞因子的表达来实现的。
