奈必洛尔减轻OVA致敏哮喘豚鼠的氧化应激反应:呼吸道保护作用的可能机制
2018/01/19
摘要
OVA致敏哮喘模型用于评价奈必洛尔对于气道反应性、肺部炎症和氧化应激标志物的疗效。奈必洛尔为第三代选择性β1肾上腺能受体阻滞剂。哮喘致敏流程被用于哮喘建模。豚鼠分为对照组、哮喘组或接受奈必洛尔哮喘组(口服7.5 mg/kg/day或15 mg/kg/day)。研究结束时,就奈必洛尔呼吸、抗炎和抗氧化作用进行评估。相较于对照组,哮喘组豚鼠气道阻力、气道组胺高反应性、白细胞全计数和绝对计数、肿瘤坏死因子-α,BALF中IL-6,肺脂质过氧化物酶和超氧化物歧化酶、谷胱甘肽均显著增加。此外,肺内皮氮氧化物合成酶(eNOS)显著增加,而诱导性氮氧化物合成酶(iNOS)mRNA显著下降。高剂量奈必洛尔可以拮抗OVA引起的气道阻力增加,但对气道高反应性并无作用。此外,奈必洛尔具有显著抗炎和抗氧化作用,并恢复eNOS和iNOS受损的功能。综上所述,本研究提示奈必洛尔治疗有益于哮喘。
(上海交通大学医学院附属瑞金医院呼吸与危重症医学科 周剑平 万欢英 摘译)
(Can J Physiol Pharmacol. 2018 Jan 10:1-8. doi: 10.1139/cjpp-2017-0230. [Epub ahead of print])
Nebivolol attenuates oxidative stress and inflammation in a guinea pig model of ovalbumin-induced asthma: a possible mechanism for its favorable respiratory effects.
Can J Physiol Pharmacol. 2018 Jan 10:1-8. doi: 10.1139/cjpp-2017-0230. [Epub ahead of print]
Abuelezz SA et al.
Abstract
An experimental model of ovalbumin (OVA) induced asthma was used to assess the effects of nebivolol, the third-generation selective β1-adrenergic receptor blocker, on airway reactivity, lung inflammation, and oxidative stress markers. The asthma induction protocol was done by OVA sensitization and challenge. Guinea pigs were classified into control, asthmatic, or asthmatic receiving nebivolol either 7.5 or 15 mg·kg-1·day-1 orally. At the end of the study respiratory, the anti-inflammatory and antioxidative effects of nebivolol were assessed. The asthmatic group exhibited a significant increase in early and late airway resistance, airway hyperreactivity to histamine, total and absolute leucocytic count, tumor necrosis factor-α, and interleukin-6 in bronchoalveolar lavage fluid and lung lipid peroxidation and a significant decrease in superoxide dismutase and glutathione compared to the control group. Additionally, there was a significant decrease in lung endothelial nitric oxide synthase (eNOS) and a significant increase in inducible nitric oxide synthase (iNOS) mRNA expression compared to the control group. The high dose of nebivolol counteracted the increased airway resistance induced by OVA, whereas it had no effect on airway hyperresponsiveness. Moreover, nebivolol exhibited significant anti-inflammatory and antioxidant effects and restored the altered levels of eNOS and iNOS compared to the asthmatic group. Collectively, these results suggest a beneficial effect of nebivolol in asthma.
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焦虑,抑郁和哮喘控制:标准化治疗后的变化
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重症哮喘新型药物治疗