General, Visceral and Transplant Surgery, Department of Surgery, Medical University of Graz, Auenbruggerplatz 2, 8036 Graz, Austria.
Faculty of Medicine, Vilnius University, M. K. Ciurlionio 21, 03101 Vilnius, Lithuania.
Int J Mol Sci. 2021 Aug 4;22(16):8373. doi: 10.3390/ijms22168373.
Ischemia/reperfusion injury (IRI) remains a significant problem to be solved in uterus transplantation (UTx). Melatonin and glycine have been shown to possess direct cytoprotective activities, mainly due to their antioxidative and anti-inflammatory properties. The aim of this study was to investigate the protective effects of melatonin and glycine and their combination on IRI in a rat model of warm ischemia. In this study, rats were assigned to eight groups, including sham and IRI ( = 80). Melatonin and glycine alone or their combination were administered prior to 1 h of uterus ischemia followed by 1 h of reperfusion. Melatonin (50 mg/kg) was administered via gavage 2 h before IRI and glycine in an enriched diet for 5 days prior to intervention. Uterus IRI was estimated by histology, including immunohistochemistry, and biochemical tissue analyses. Histology revealed that uterus IRI was significantly attenuated by pretreatment with melatonin ( = 0.019) and glycine ( = 0.044) alone as well as their combination ( = 0.003). Uterus IRI led to increased myeloperoxidase expression, which was significantly reduced by melatonin ( = 0.004), glycine ( < 0.001) or their combination ( < 0.001). The decline in superoxide dismutase activity was significantly reduced in the melatonin ( = 0.027), glycine ( = 0.038) and combined treatment groups ( = 0.015) when compared to the IRI control group. In conclusion, melatonin, glycine and their combination significantly reduced oxidative stress-induced cell damage after IRI in a small animal warm ischemia model, and, therefore, clinical studies are required to evaluate the protective effects of these well-characterized substances in uterus IRI.
缺血再灌注损伤(IRI)仍然是子宫移植(UTx)中需要解决的一个重大问题。褪黑素和甘氨酸已被证明具有直接的细胞保护活性,主要归因于它们的抗氧化和抗炎特性。本研究旨在探讨褪黑素、甘氨酸及其联合应用对大鼠热缺血模型中 IRI 的保护作用。
在这项研究中,将大鼠分为 8 组,包括假手术组和 IRI 组(每组 80 只)。在子宫缺血 1 小时前给予褪黑素和甘氨酸单独或联合治疗,然后进行 1 小时的再灌注。在 IRI 前 2 小时通过灌胃给予褪黑素(50mg/kg),在干预前 5 天通过富含甘氨酸的饮食给予甘氨酸。通过组织学、包括免疫组织化学和生化组织分析来评估子宫 IRI。
组织学结果显示,褪黑素( = 0.019)和甘氨酸( = 0.044)单独以及联合预处理显著减轻了子宫 IRI( = 0.003)。子宫 IRI 导致髓过氧化物酶表达增加,而褪黑素( = 0.004)、甘氨酸( < 0.001)或联合治疗( < 0.001)显著降低了其表达。与 IRI 对照组相比,超氧化物歧化酶活性的下降在褪黑素( = 0.027)、甘氨酸( = 0.038)和联合治疗组( = 0.015)中显著降低。
综上所述,在小型动物热缺血模型中,褪黑素、甘氨酸及其联合应用显著减轻了 IRI 引起的氧化应激诱导的细胞损伤,因此需要进行临床研究来评估这些特征明确的物质对子宫 IRI 的保护作用。