Department of Physiology, Faculty of Medicine, Istanbul Yeni Yuzyil University, Istanbul 34010, Turkey.
Department of Physiology, Istanbul Medical Faculty, Istanbul University, Istanbul 34093, Turkey.
Exp Biol Med (Maywood). 2022 Jun;247(12):1080-1089. doi: 10.1177/15353702221084933. Epub 2022 Apr 2.
We aimed to investigate the effects of melatonin administered before and during endotoxemia on the lung tissue of rats, cytokine, YKL-40, matrix metalloproteinase (MMP) and inhibitor levels, oxidative stress parameters, and energy balance. Sepsis was induced with lipopolysaccharide (LPS), the cell wall molecule of gram negative bacteria. Rats were divided into four groups, Control, LPS (Escherichia coli O127:B8, 20 mg/kg), melatonin (10 mg/kg), and melatonin+LPS (M+LPS). After injections, lung tissues samples were taken for experimental analyses. YKL-40, thiobarbituric acid reactive substances (TBARS), glutathione reductase (GR), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) enzymes levels were measured, high-energy components were analyzed; tumor necrosis factor-alpha (TNF-α), MMP-2, YKL-40, MMP-9, myeloperoxidase (MPO), tissue inhibitors of matrix metalloproteinase (TIMP)-1, and interleukin (IL)-10 immunoreactivities were investigated. In LPS group, YKL-40, creatine phosphate (both, < 0.05), SOD, GR, adenosine mono-phophate (AMP), adenosine tri-phosphate (ATP) (for all, < 0.01) were significantly decreased, while TBARS and adenosine di-phosphate (ADP) levels were increased ( < 0.01, < 0.05; respectively) compared to other groups. MMP-2 and -9, TIMP-1, TNF-α, IL-10, and MPO immunoreactivity were investigated in LPS group. On the contrary, in M+LPS group, MMP-9, TIMP-1 immunoreactivities were not found and IL-10 and MMP-2 immunoreactivities were found with little involvement. In M+LPS group, YKL-40, GR, AMP, ATP, creatine phosphate (for all, < 0.05), and SOD ( < 0.01) levels were significantly increased and TBARS levels were decreased ( < 0.05). In our study, we suggest that melatonin exerts a protective and curative effect by reducing the matrix metalloproteinase levels responsible for tissue damage balance, stimulating the release of antioxidant enzymes, regulating cytokines and energy balance during endotoxemia.
我们旨在研究内毒素血症前和期间给予褪黑素对大鼠肺组织、细胞因子、 YKL-40、基质金属蛋白酶（MMP）和抑制剂水平、氧化应激参数和能量平衡的影响。内毒素血症由脂多糖（LPS）诱导，LPS 是革兰氏阴性菌细胞壁分子。大鼠分为四组：对照组、LPS（大肠杆菌 O127:B8，20mg/kg）、褪黑素（10mg/kg）和褪黑素+LPS（M+LPS）。注射后，取肺组织样本进行实验分析。测量 YKL-40、硫代巴比妥酸反应物质（TBARS）、谷胱甘肽还原酶（GR）、谷胱甘肽过氧化物酶（GSH-Px）、超氧化物歧化酶（SOD）酶水平，分析高能成分；研究肿瘤坏死因子-α（TNF-α）、MMP-2、YKL-40、MMP-9、髓过氧化物酶（MPO）、基质金属蛋白酶组织抑制剂（TIMP）-1 和白细胞介素（IL）-10 免疫反应性。在 LPS 组中，与其他组相比，YKL-40 和磷酸肌酸（均<0.05）、SOD、GR、单磷酸腺苷（AMP）、三磷酸腺苷（ATP）（均<0.01）显著降低，而 TBARS 和二磷酸腺苷（ADP）水平升高（均<0.01，<0.05）。在 LPS 组中研究了 MMP-2 和 -9、TIMP-1、TNF-α、IL-10 和 MPO 免疫反应性。相反，在 M+LPS 组中，未发现 MMP-9、TIMP-1 免疫反应性，而发现了 IL-10 和 MMP-2 免疫反应性，且参与程度较低。在 M+LPS 组中，YKL-40、GR、AMP、ATP、磷酸肌酸（均<0.05）和 SOD（<0.01）水平显著升高，TBARS 水平降低（<0.05）。在我们的研究中，我们认为褪黑素通过降低负责组织损伤平衡的基质金属蛋白酶水平、刺激抗氧化酶释放、调节细胞因子和内毒素血症期间的能量平衡来发挥保护和治疗作用。
