首页> 外文期刊>American Journal of Physiology >Enalapril protects mice from pulmonary hypertension by inhibiting TNF-mediated activation of NF-kappaB and AP-1.
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Enalapril protects mice from pulmonary hypertension by inhibiting TNF-mediated activation of NF-kappaB and AP-1.

机译:依那普利通过抑制TNF介导的NF-κB和AP-1的活化,保护小鼠免受肺动脉高压的影响。

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The present study was undertaken to investigate the effects of treatment with the angiotensin-converting enzyme (ACE) inhibitor enalapril in a mouse model of pulmonary hypertension induced by bleomycin. Bleomycin-induced lung injury in mice is mediated by enhanced tumor necrosis factor-alpha (TNF) expression in the lung, which determines the murine strain sensitivity to bleomycin, and murine strains are sensitive (C57BL/6) or resistant (BALB/c). Bleomycin induced significant pulmonary hypertension in C57BL/6, but not in BALB/c, mice; average pulmonary arterial pressure (PAP) was 26.4 +/- 2.5 mmHg (P < 0.05) vs. 15.2 +/- 3 mmHg, respectively. Bleomycin treatment induced activation of nuclear factor (NF)-kappaB and activator protein (AP)-1 and enhanced collagen and TNF mRNA expression in the lung of C57BL/6 but not in BALB/c mice. Double TNF receptor-deficient mice (in a C57BL/6 background) that do not activate NF-kappaB or AP-1 in response to bleomycin did not develop bleomycin-induced pulmonary hypertension (PAP 14 +/- 3 mmHg). Treatment of C57BL/6 mice with enalapril significantly (P < 0.05) inhibited the development of pulmonary hypertension after bleomycin exposure. Enalapril treatment inhibited NF-kappaB and AP-1 activation, the enhanced TNF and collagen mRNA expression, and the deposition of collagen in bleomycin-exposed C57BL/6 mice. These results suggest that ACE inhibitor treatment decreases lung injury and the development of pulmonary hypertension in bleomycin-treated mice.
机译:进行本研究以研究血管紧张素转化酶(ACE)抑制剂依那普利在博来霉素诱发的肺动脉高压小鼠模型中的治疗作用。博来霉素诱导的小鼠肺损伤是由肺中肿瘤坏死因子-α(TNF)表达增强介导的,这决定了鼠类菌株对博来霉素的敏感性,鼠类菌株是敏感的(C57BL / 6)或耐药的(BALB / c) 。博来霉素可在C57BL / 6小鼠中引起明显的肺动脉高压,但在BALB / c小鼠中则不会。平均肺动脉压(PAP)分别为26.4 +/- 2.5 mmHg(P <0.05)与15.2 +/- 3 mmHg。博来霉素治疗可诱导C57BL / 6的肺中核因子(NF)-κB和激活蛋白(AP)-1的活化,并增强胶原和TNF mRNA表达,而BALB / c小鼠则不然。不响应博来霉素而激活NF-κB或AP-1的双重TNF受体缺陷型小鼠(在C57BL / 6背景中)未发展出博来霉素诱导的肺动脉高压(PAP 14 +/- 3 mmHg)。依那普利对C57BL / 6小鼠的治疗显着(P <0.05)抑制了博来霉素暴露后肺动脉高压的发展。依那普利治疗可抑制博来霉素暴露的C57BL / 6小鼠的NF-κB和AP-1活化,增强的TNF和胶原mRNA表达以及胶原沉积。这些结果表明ACE抑制剂治疗减少了博来霉素治疗的小鼠的肺损伤和肺动脉高压的发展。

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