NF-κB 转录因子激活在代谢综合征下骨骼肌连接组织成分退化过程中的作用

O. Akimov, A. Mykytenko, A. Mischenko, V. Kostenko
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引用次数: 0

摘要

结缔组织包括细胞和非细胞元素,在各种器官和组织的众多病理过程中发挥着重要作用。在骨骼肌组织内,细胞外基质不仅起着结构和支撑作用,而且是一个复杂的多成分系统,具有多种调节功能。目前,对代谢综合征发生过程中转录因子 NF-κB 的激活对骨骼肌细胞外基质成分的定量和定性组成的影响研究不足。本研究旨在探讨吡咯烷二硫代氨基甲酸铵对代谢综合征大鼠股二头肌中糖胺聚糖浓度、糖胺聚糖单个组分浓度、游离 L-氧脯氨酸和硅酸含量的影响。研究对象是 24 只体重为 200-260 克的雄性 Wistar 大鼠,随机分为 4 组,每组 6 只。第一组为对照组;第二组为代谢综合征模型组。在标准饲养室饮食中添加 20% 的果糖溶液,作为唯一的饮用水源,从而再现代谢综合征。代谢综合征模拟期为 60 天。第三组接受吡咯烷二硫代氨基甲酸铵治疗,剂量为 76 毫克/千克,腹腔注射(i/p),每周三次,持续 60 天。第四组接受吡咯烷二硫代氨基甲酸铵和代谢综合征模型的联合治疗。在股二头肌 10%的匀浆中,评估了糖胺聚糖的总浓度、糖胺聚糖中肝素-天冬氨糖部分、糖胺聚糖中角蛋白-麦角糖部分、糖胺聚糖中软骨素部分的浓度,以及游离 L-氧脯氨酸和硅酸的含量。与代谢综合征组相比,在代谢综合征模型下引入吡咯烷二硫代氨基甲酸铵可使糖胺聚糖的总浓度降低 9.2%。在这些条件下,与代谢综合征组相比,肝素-天冬酰胺部分的浓度增加了 121.1%,角蛋白-麦角固醇部分的浓度降低了 32.8%,软骨素部分的浓度降低了 38.7%。与代谢综合征组相比,股二头肌中游离 L-氧脯氨酸和硫辛酸的浓度分别下降了 19.8%和 24.4%。在代谢综合征建模的背景下,通过腹腔注射吡咯烷二硫代氨基甲酸铵阻断转录因子 NF-κB 的激活,可减少糖蛋白和蛋白聚糖的解聚、降低胶原蛋白溶解的强度,并导致糖胺聚糖各部分浓度的重新分布,其特点是大鼠股二头肌中肝素-天冬酰胺部分含量增加,软骨素和角蛋白-麦角固醇部分含量减少。
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ROLE OF NF-κB TRANSCRIPTION FACTOR ACTIVATION IN THE PROCESSES OF CONNECTIVE TISSUE COMPONENTS DEGRADATION IN SKELETAL MUSCLES UNDER METABOLIC SYNDROME
Connective tissue, encompassing both cellular and non-cellular elements, plays an important role in the progression of numerous pathological processes across various organs and tissues. Within skeletal muscle tissue, the extracellular matrix not only plays a structural and supporting function, but it is a complex multicomponent system that performs a number of regulatory functions. At present, the effect of activation of the transcription factor NF-κB on the quantitative and qualitative composition of the components of the extracellular matrix in skeletal muscles under metabolic syndrome development is insufficiently studied. The aim of this work is to study the effect of ammonium pyrrolidinedithiocarbamate on the concentration of glycosaminoglycans, the concentration of individual fractions of glycosaminoglycans, the content of free L-oxyproline and sialic acids in the biceps femoris muscle of rats under metabolic syndrome. The study was conducted on 24 male Wistar rats weighing 200-260 g, which were randomly divided into 4 groups of 6 animals each. The first was control; the second made up the metabolic syndrome modeling group. Metabolic syndrome was reproduced by adding a 20% fructose solution to the standard vivarium diet as the only source of drinking water. Metabolic syndrome was modelled for 60 days. The third group received ammonium pyrrolidinedithiocarbamate administration at a dose of 76 mg/kg intraperitoneally (i/p) three times a week for 60 days. The fourth group underwent combined treatment involving the administration of both ammonium pyrrolidinedithiocarbamate and metabolic syndrome modeling. In a 10% homogenate of the biceps femoris muscle, the total concentration of glycosaminoglycans, the concentration of the heparin-heparan fraction of glycosaminoglycans, the keratan-dermatan fraction of glycosaminoglycans, the chondroitin fraction of glycosaminoglycans, and the content of free L-oxyproline and sialic acids were assessed. The introduction of ammonium pyrrolidinedithiocarbamate under metabolic syndrome modelling led to a decrease in the total concentration of glycosaminoglycans by 9.2% compared to the metabolic syndrome group. Under these conditions, the concentration of the heparin-heparan fraction increased by 121.1%, the keratan-dermatan fraction decreased by 32.8%, and the concentration of the chondroitin fraction decreased by 38.7% compared to the metabolic syndrome group. The concentration of free L-oxyproline and sialic acids in the biceps femoris muscle decreased by 19.8% and 24.4%, respectively, compared to the metabolic syndrome group. Blockade of activation of the transcription factor NF-κB by intraperitoneal administration of ammonium pyrrolidinedithiocarbamate against the background of metabolic syndrome modelling leads to a decrease in the depolymerization of glycoproteins and proteoglycans, reduces the intensity of collagenolysis and leads to a redistribution of concentrations of individual fractions of glycosaminoglycans, characterized by an increase in the content of the heparin-heparan fraction and a decrease in chondroitin and keratan-dermatan fractions in the biceps femoris muscle of rats.
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