瘦素介导气道上皮细胞调控肥胖相关的气道高反应  

Obesity related-airway hyperresponsiveness was regulated by leptin mediated airway epithelial cells

作　　者：秦岭[1] 宋智[2] 文赛兰[3] 胡成平[1] 

机构地区：[1]中南大学湘雅医院呼吸内科,长沙410008 [2]中南大学湘雅三医院普外科,长沙410013 [3]中南大学湘雅二医院病理科,长沙410008

出　　处：《国际呼吸杂志》2014年第23期1783-1788,共6页International Journal of Respiration

基　　金：湖南省科技厅科研重点项目（2012FJ4375）;湖南省高校创新平台开放基金（14K108）;中南大学青年教师助推项目（2012QNZT111）

摘　　要：目的肥胖增加了支气管哮喘（简称哮喘）发病的危险，但具体机制不明确。本研究通过观察肥胖小鼠血清瘦素浓度和气道激发试验后肺功能的变化以及瘦素对人支气管上皮细胞（HBECs）的促炎作用来明确瘦素在肥胖相关的气道高反应中的作用。方法①健康雌性Ba1b／c小鼠20只，随机分为对照组（喂予基础饲料）和肥胖组（喂予高脂高糖食物）。30d后记录小鼠的体质量和增长率，乙酰甲胆碱激发后检测各组小鼠激发前后的潮气量（TV）、气道阻力（AR）与肺顺应性（Cdyn）。ELISA测定血清瘦素水平。②将重组人瘦素（rhLEP）作用于HBECs，分别为对照组、0．2mg／L05mg／L、1mg／L干预组，24h后ELISA检测上清液中IL-6和IL-8的浓度，Realtime—PCR观察HBECs中核因子xB（NFwB）和细胞黏附分子-1（ICAM-1）mRNA的表达。结果①高脂高糖食物喂养后，肥胖组小鼠体质量、体质量增长率和血清瘦素浓度均明显高于对照组。肺功能测定显示：激发前，肥胖组的AR大于对照组。乙酰甲胆碱激发后，肥胖组AR的水平和升高幅度都明显大于对照组。TV和Cydn在各组之间以及激发前后差异均无统计学意义。②rhLEP作用于HBECs后，rhLEP干预组细胞七清液内IL-6和1L-8水平以及细胞内ICAM-1表达均明显高于对照组。NF-KB的表达与对照组差异无明显统计学意义。结论瘦素可能是通过促进HBECs释放炎性因子和对炎性细胞的募集作用在肥胖相关的气道高反应中起作用。Objective Clinical studies found that obesity increased the risk of asthma, but its mechanism remains unclear. In this study,we explored the level of serum leptin and pulmonary function before/after provocation test in obesity mice and pro-inflammatory role of airway epithelial cells under leptin treatment, in order to clarify the role of leptin in obesity related-airway hyperresponsiveness. Methods Twenty female Balb/c mice are randomly divided into 2 groups： control group fed with normal foods, Fatty-diet Group fed with high fatty and high sugar foods. After 30 days, the animals, whose bodyweights and their growing rate were recorded, were aroused with methacholine （Mch） and then tested for airway resistance （AR）,tidal volume （TV） and dynamic compliance （Cydn）. Blood was harvested for determining levels of Ieptin by ELISA. （2）Human bronchial epithelial cell line （HBECs） were treated by recombinant human leptin （rhLEP） at various concentrations （0.2 mg/L,0.5 mg/L and 1 mg/L）. After 24 h,human IL 6, IL-8 concentrations in supernatants from HBECs were determined using ELISA kits and expression of NF-kB and ICAM 1 mRNA in HBECs were quantified by real-time PCR. Results O After feeding with high fatty and high sugar foods, the weight, its growth rate and the level of serum leptin in obese mice were significantly higher than those in Control. The test of pulmonary functionshowed that,in obese group,RL before and after stimulation and its elevated extent was all greater than those in control. There was no obvious difference of TV and Cydn between two groups. （3）After stimulated by rhLEP,the levels of IL 6 and IL-8 in supernatants and ICAM-1 expression from HBECs were higher than control. But NF-kB expression was not changed. Conclusions Leptin may play an important role in obesity related airway hyperresponsiveness through promoting HBECs recruit inflammatory cells and release eytokines.

关 键 词：瘦素 肥胖 支气管上皮细胞 气道高反应 

分 类 号：R544.1[医药卫生—心血管疾病]