Claveles Casas F N, Barrera F S, Lopez C M, Chacon I Del V, Di Sciullo M P, Ramirez D C, Gomez Mejiba S E
Laboratory of Experimental & Translational Medicine. IMIBIO-SL, CONICET-National University of San Luis, San Luis, 5700 San Luis, Argentina.
Laboratory of Experimental Therapeutics & Nutrition. IMIBIO-SL, CONICET-National University of San Luis, San Luis, 5700 San Luis, Argentina.
Open J Pharm Sci Res. 2019;1(1):123-133. doi: 10.36811/ojpsr.2019.110006. Epub 2019 Aug 10.
Epidemiology and experimental models have shown a close link between adipose tissue inflammation, systemic inflammation and pulmonary neutrophilic inflammation, which predispose obese patients to pulmonary diseases, obesity-associated co-morbidities and cancer. Increased content and activation of neutrophils in the lung microvasculature, resulting from peripheral activation of neutrophils, and increased adhesion of neutrophils to the lung microvasculature are important factors explaining the increased susceptibility of obese patients towards respiratory diseases and loss of insulin sensitivity. Mechanism-based therapies to break this link are urgently needed to reduce pulmonary damage in obesity, due to the growing prevalence of obesity world-wide. Current research suggests that these approaches should be focused on, one or more of the following: reduction of macrophage activation at the adipose tissue, healthy growing of adipose tissue by induction of Nrf-2, inhibition of NF-κB activation, reduction of circulating neutrophil activation, blocking adhesins/selectins, inhibition of neutrophil activation by targeting NADPH oxidase-2 activation, inhibition of myeloperoxidase activity and scavenging of hypochlorous acid. These strategies are expected to reduce adipose tissue inflammation, peripheral inflammation, pulmonary neutrophilic inflammation and obesity-associated co-morbidities.
流行病学和实验模型表明，脂肪组织炎症、全身炎症与肺部中性粒细胞炎症之间存在密切联系，这使肥胖患者易患肺部疾病、肥胖相关合并症和癌症。肺部微血管中中性粒细胞含量和活性的增加，源于中性粒细胞的外周激活，以及中性粒细胞与肺部微血管黏附的增加，是解释肥胖患者对呼吸系统疾病易感性增加和胰岛素敏感性丧失的重要因素。由于全球肥胖患病率不断上升，迫切需要基于机制的疗法来打破这种联系，以减少肥胖引起的肺部损伤。目前的研究表明，这些方法应集中在以下一个或多个方面：减少脂肪组织中巨噬细胞的激活、通过诱导Nrf-2促进脂肪组织健康生长、抑制NF-κB激活、减少循环中性粒细胞的激活、阻断黏附素/选择素、通过靶向NADPH氧化酶-2激活抑制中性粒细胞激活、抑制髓过氧化物酶活性以及清除次氯酸。这些策略有望减少脂肪组织炎症、外周炎症、肺部中性粒细胞炎症以及肥胖相关合并症。
