Kowalczyk Agata, Jeleń Agnieszka, Żebrowska Marta, Balcerczak Ewa, Gorąca Anna
Department of Cardiovascular Physiology, Chair of Experimental and Clinical Physiology, Medical University of Lodz, 6/8 Mazowiecka Street, 92-215 Lodz, Poland.
Laboratory of Molecular Diagnostic and Pharmacogenomics, Department of Pharmaceutical Biochemistry and Molecular Diagnostic, Medical University of Lodz, 1 Muszynskiego Street, 90-151 Lodz, Poland.
Oxid Med Cell Longev. 2016;2016:2356853. doi: 10.1155/2016/2356853. Epub 2015 Dec 28.
Little is understood of skeletal muscle tissue in terms of oxidative stress and inflammation. Endothelin-1 is an endogenous, vasoconstrictive peptide which can induce overproduction of reactive oxygen species and proinflammatory cytokines. The aim of this study was to evaluate whether BQ123, an endothelin-A receptor antagonist, influences the level of TNF-α, IL-6, SOD-1, HO-1, Nrf2 mRNA, and NF-κB subunit RelA/p65 mRNA in the femoral muscle obtained from endotoxemic rats. Male Wistar rats were divided into 4 groups (n = 6) and received iv (1) saline (control), (2) LPS (15 mg/kg), (3) BQ123 (1 mg/kg), (4) BQ123 (1 mg/kg), and LPS (15 mg/kg, resp.) 30 min later. Injection of LPS led to significant increase in levels of RelA/p65 mRNA, TNF-α, and IL-6, while content of SOD-1, HO-1, and Nrf2 mRNA was unchanged. Administration of BQ123 prior to LPS challenge resulted in a significant reduction in RelA/p65 mRNA, TNF-α, and IL-6 levels, as well as markedly elevated concentrations of SOD-1, HO-1, and Nrf2 mRNA. BQ123 appears to enhance antioxidant defense and prevent production of TNF-α and IL-6 in skeletal muscle of LPS-treated rat. In conclusion, endothelin-A receptor antagonism exerts significant impact on the skeletal muscle favouring anti-inflammatory effects and protection against oxidative stress.
就氧化应激和炎症而言，人们对骨骼肌组织了解甚少。内皮素-1是一种内源性血管收缩肽，可诱导活性氧和促炎细胞因子的过量产生。本研究的目的是评估内皮素-A受体拮抗剂BQ123是否会影响内毒素血症大鼠股肌中TNF-α、IL-6、SOD-1、HO-1、Nrf2 mRNA和NF-κB亚基RelA/p65 mRNA的水平。雄性Wistar大鼠分为4组（n = 6），静脉注射：（1）生理盐水（对照组），（2）脂多糖（15 mg/kg），（3）BQ123（1 mg/kg），（4）30分钟后分别注射BQ123（1 mg/kg）和脂多糖（15 mg/kg）。注射脂多糖导致RelA/p65 mRNA、TNF-α和IL-6水平显著升高，而SOD-1、HO-1和Nrf2 mRNA的含量未发生变化。在脂多糖攻击前给予BQ123可导致RelA/p65 mRNA、TNF-α和IL-6水平显著降低，以及SOD-1、HO-1和Nrf2 mRNA浓度显著升高。BQ123似乎可增强抗氧化防御，并防止脂多糖处理的大鼠骨骼肌中TNF-α和IL-6的产生。总之，内皮素-A受体拮抗作用对骨骼肌有显著影响，有利于抗炎作用并保护其免受氧化应激。
