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近日，研究人员发现雌性老鼠体内对细菌性肺炎增强的抵抗力与雌性体内雌激素激活酶有关。
女性有天生比男性更强的抵抗呼吸道感染的能力。目前，一个国际科学家小组已经表明，雌性老鼠体内对细菌性肺炎增强的抵抗力与一氧化氮合酶3(NOS3)有关联。最终实验也表明，雌性通过释放荷尔蒙雌激素激活这种酶。
Lester Kobzik 教授领导的研究小组引入肺炎链球菌进入到老鼠的肺部来模仿自然发生的吸入细菌，就像我们的呼吸一样。相比较正常的雄性老鼠，用雌激素治疗雌性小鼠和雄性小鼠能够迅速从它们的肺部清除细菌。在体外进行测试中，雌性肺部的宿主防御细胞能更好地杀死这些细菌和其他细菌(大肠杆菌和金黄色葡萄球菌)。
科学家们随后设计了另一组雄性和雌性小鼠的实验，删除了负责生产NOS3的基因。他们发现，删除这个基因意味着雌性小鼠不再具有抗感染的能力。研究小组希望将来利用这些知识可以用来增强抵抗常见的和严重的肺部感染等疾病。
“在季节性或大流行性流感期间，为减少感染继发性细菌性肺炎的风险，这项工作可能特别有用”Lester Kobzik教授说，“我们很高兴靶向NOS3的药物已经准用，该药用在实验的小鼠模型中确实可以提高抗肺炎效果。”
Female resistance to pneumonia identifies lung macrophage nitric oxide Synthase-3 as a therapeutic target
1.Zhiping Yang, Yuh-Chin T Huang, Henry Koziel, Rini de Crom, Hartmut Ruetten, Paulus Wohlfart, Reimar W Thomsen, Johnny Kahlert, Henrik Toft Sørensen, Szczepan Jozefowski, Amy Colby, Lester Kobzik.
Abstract To identify new approaches to enhance innate immunity to bacterial pneumonia, we investigated the natural experiment of gender differences in resistance to infections. Female and estrogen-treated male mice show greater resistance to pneumococcal pneumonia, seen as greater bacterial clearance, diminished lung inflammation and better survival. In vitro, lung macrophages from female mice and humans show better killing of ingested bacteria. Inhibitors and genetically altered mice identify a critical role for estrogen-mediated activation of lung macrophage nitric oxide synthase-3 (NOS3). Epidemiologic data show decreased hospitalization for pneumonia in women receiving estrogen or statins (known to activate NOS3). Pharmacologic targeting of NOS3 with statins or another small-molecule compound (AVE3085) enhanced macrophage bacterial killing, improved bacterial clearance and increased host survival in both primary and secondary (post-influenza) pneumonia. The data identify a novel mechanism for host defense via NOS3 and suggest a potential therapeutic strategy to reduce secondary bacterial pneumonia after influenza.
转载地址：http://news.bioon.com/article/6660274.html
