Department of Physiology and Pathophysiology, Medical University of Varna, Varna 9002, Bulgaria.
Department of Preclinical and Clinical Sciences, Medical University of Varna, Varna 9002, Bulgaria.
Molecules. 2018 Mar 24;23(4):749. doi: 10.3390/molecules23040749.
Melatonin, a basic secretory pineal gland product, is a nontoxic, multifunctional molecule. It has antioxidant and anti-apoptotic activities and protects tissues from injury. The objective of the present study was to determine the molecular mechanism of melatonin anti-apoptotic effect on gastric injury in a rat burn model. We hypothesized that melatonin gastric protection may be related to the activation of transcription erythroid 2-related factor 2 (Nrf2). Using a 30% total body surface area (TBSA) rat burn model, melatonin (10 mg/kg, i.p.) was injected immediately and 12 h after thermal skin injury. Via light immunohistochemistry, we determined the tissue level of 4-hydroxy-2-nonenal (4-HNE) as a marker of lipid peroxidation, Bcl-2 and Bax as apoptosis-related proteins, and Nrf2. Results are presented as medians (interquartile range (IQR)). Thermal trauma in burned animals, compared with the controls, increased the expression of pro-apoptotic Bax protein (1.37 (0.94-1.47)), decreased anti-apoptotic Bcl-2 protein (1.16 (1.06-1.23), < 0.001) in epithelial cells, and elevated Bax/Bcl-2 ratios ( < 0.05). Tissue 4-HNE and Nrf2 levels were increased following severe burns (1.55 (0.98-1.61) and 1.16 (1.01-1.25), < 0.05, respectively). Melatonin significantly decreased 4-HNE (0.87 (0.74-0.96), < 0.01) and upregulated Nrf2 (1.55 (1.52-1.65), < 0.001) levels. It also augmented Bax (1.68 (1.5-1.8), < 0.001) and Bcl-2 expressions (1.96 (1.89-2.01), < 0.0001), but reduced Bax/Bcl-2 ratios ( < 0.05). Our results suggest that experimental thermal trauma induces oxidative gastric mucosal injury. Melatonin manifests a gastroprotective effect through Nrf2 activation, lipid peroxidation attenuation, and Bax/Bcl-2 ratio modification as well.
褪黑素是松果腺分泌的一种基本的非毒性多功能分子。它具有抗氧化和抗细胞凋亡作用，可以保护组织免受损伤。本研究的目的是确定褪黑素对烫伤大鼠胃损伤的抗凋亡作用的分子机制。我们假设褪黑素的胃保护作用可能与转录激活因子 2 相关因子 2（Nrf2）的激活有关。使用 30%总体表面积（TBSA）大鼠烫伤模型，在热皮肤损伤后立即和 12 小时内注射褪黑素（10mg/kg，腹腔内注射）。通过光免疫组织化学法，我们测定了脂质过氧化标志物 4-羟基-2-壬烯醛（4-HNE）、凋亡相关蛋白 Bcl-2 和 Bax 以及 Nrf2 的组织水平。结果以中位数（四分位距（IQR））表示。与对照组相比，烫伤动物的热创伤增加了上皮细胞中促凋亡 Bax 蛋白的表达（1.37（0.94-1.47）），降低了抗凋亡 Bcl-2 蛋白的表达（1.16（1.06-1.23），<0.001），并升高了 Bax/Bcl-2 比值（<0.05）。严重烧伤后，组织 4-HNE 和 Nrf2 水平升高（1.55（0.98-1.61）和 1.16（1.01-1.25），<0.05）。褪黑素显著降低了 4-HNE（0.87（0.74-0.96），<0.01）并上调了 Nrf2（1.55（1.52-1.65），<0.001）水平。它还增加了 Bax（1.68（1.5-1.8），<0.001）和 Bcl-2 的表达（1.96（1.89-2.01），<0.0001），但降低了 Bax/Bcl-2 比值（<0.05）。我们的结果表明，实验性热创伤引起胃黏膜氧化损伤。褪黑素通过 Nrf2 激活、脂质过氧化减弱和 Bax/Bcl-2 比值改变来发挥胃保护作用。
