BQ123 Stimulates Skeletal Muscle Antioxidant Defense via Nrf2 Activation in LPS-Treated Rats.
BQ123 Stimulates Skeletal Muscle Antioxidant Defense via Nrf2 Activation in LPS-Treated Rats.
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BQ123通过在LPS处理的大鼠中通过NRF2激活刺激骨骼肌抗氧化剂防御。
DOI：
10.1155/2016/2356853
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发表时间：
2016
影响因子：
--
通讯作者：
Gorąca A
中科院分区：
文献类型：
--
作者：
Kowalczyk A;Jeleń A;Żebrowska M;Balcerczak E;Gorąca A
骨骼肌组织在氧化应激和炎症方面了解甚少。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度产生。本研究旨在探讨内皮素A受体拮抗剂BQ 123对内毒素血症大鼠股肌TNF-α、IL-6、SOD-1、HO-1、Nrf 2 mRNA和NF-κB B亚单位RelA/p65 mRNA表达的影响。雄性Wistar大鼠分为4组（n = 6），分别静脉注射（1）生理盐水（对照组）、（2）LPS（15 mg/kg）、（3）BQ 123（1 mg/kg）、（4）BQ 123（1 mg/kg）和LPS（15 mg/kg）。半个时辰后。注射LPS后，RelA/p65 mRNA、TNF-α和IL-6水平显著升高，而SOD-1、HO-1和Nrf 2 mRNA水平无明显变化。在LPS攻击前给予BQ 123导致RelA/p65 mRNA、TNF-α和IL-6水平显著降低，以及SOD-1、HO-1和Nrf 2 mRNA浓度显著升高。BQ 123似乎增强LPS处理的大鼠骨骼肌中的抗氧化防御并防止TNF-α和IL-6的产生。总之，内皮素-A受体拮抗剂对骨骼肌产生显著影响，有利于抗炎作用和保护免受氧化应激。
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.