辛伐他汀对肥胖哮喘小鼠气道炎症的作用及其机制

Effect of Simvastatin on airway inflammation in obese asthma mice and its mechanism

摘要:

目的  探讨辛伐他汀对肥胖哮喘小鼠气道炎症的作用及其机制。方法  将60只C57BL/6J小鼠随机分为空白对照组、肥胖哮喘组、地塞米松治疗组和辛伐他汀治疗组。其中，肥胖哮喘组、地塞米松治疗组、辛伐他汀治疗组小鼠采用卵蛋白致敏、激发的方法和高脂饮食诱导建立肥胖哮喘模型。地塞米松治疗组每日给予地塞米松（0.5 mg/kg）饮水干预，辛伐他汀治疗组每日给予辛伐他汀（40 mg/kg）饮水干预，其余两组正常饮水。治疗4周后，计数存活小鼠，采外周血生化分析仪测定血糖、血脂、肝功能水平；收集支气管肺泡灌洗液，计数支气管肺泡灌洗液中白细胞总数及各炎症细胞所占比例；肺病理切片观察小鼠气道炎症和结构变化。结果  肥胖哮喘组、地塞米松治疗组、辛伐他汀治疗组气道炎症评分、回抽收集灌洗液中白细胞总数及中性粒细胞百分比、血清总胆固醇水平均较空白对照组升高，其中辛伐他汀治疗组上述指标较肥胖哮喘组、地塞米松治疗组下降，差异有统计学意义（P <0.05）。且总胆固醇水平与支气管肺泡灌洗液中中性粒细胞百分比呈正相关（r =0.724，P =0.020）。结论  辛伐他汀治疗可以减轻肥胖哮喘的气道炎症，改善哮喘病情，这一作用与其降低血脂水平有一定关系。

Abstract:

Objective To investigate the effect of Simvastatin on airway inflammation in obese asthma mice and the mechanism. Methods Sixty C57BL/6J mice were randomly divided into four groups: blank control group (group A), obese asthma group (group B), Dexamethasone treatment group (group C) and Simvastatin treatment group (group D). The mice fed with high-fat diet were sensitized and challenged with ovalbumin (OVA) to establish the model of chronic obese asthma. The mice of the group C were treated with Dexamethasone (0.5 mg/kg) daily, and the mice of the group D were treated with Simvastatin (40 mg/kg) daily in 4 weeks. After last OVA challenge, the survival number of mice and mice reaction during challenge in each group were recorded. After the mice were anesthetized, blood, bronchoaveolar lavage fluid (BALF) and lung tissue were collected and kept respectively. The serum FBG, TC, TG, AST and ALT were measured by biochemical analyzer. The total number of white cells and the proportion of leukocytes, eosinophils, neutrophils and macrophages in the BALF were counted under microscope. The structural changes and inflammation in the lung tissue sections of mice were observed and recorded. Results The airway inflammation score, the total number of white blood cells and neutrophil proportion in the BALF and serum TC levels were higher in the groups B, C and D than those in the group A; the above indexes in the group D significantly decreased compared with the groups B and C (P < 0.05). Serum TC level was positively correlated with the proportion of neutrophils in the BALF (r = 0.724, P = 0.020). Conclusions Simvastatin can alleviate airway inflammation and asthma attack partly by correcting lipid disorder.