雷公藤红素对肥胖型哮喘气道高反应的影响

Effect of Celastrol on Airway Hyperresponsiveness in Obese Asthma Mice

目的探讨雷公藤红素(celastrol)对肥胖型哮喘小鼠气道高反应的影响。方法雄性C57BL/6小鼠30只,随机分为正常对照组、哮喘组、肥胖组、肥胖型哮喘组和雷公藤红素干预的肥胖型哮喘组(简称干预组)共5组。肥胖型哮喘组和干预组予以高脂饲料(HFD)喂养16周,于第13周起第1天和第13天腹腔注射卵清蛋白/氢氧化铝[OVA/AL(OH)3]致敏,第25~31天连续7天雾化吸入OVA激发,干预组在每次雾化吸入前30min口服celastrol(10mg/kg)。哮喘组进行普通饲料喂养+OVA致敏激发。肥胖组进行高脂饲料喂养+生理盐水致敏激发。正常组进行普通饲料喂养+生理盐水致敏激发。运用小鼠肺功能仪检测小鼠气道高反应性(AHR)的指标呼吸气道阻力(Rn),进行相关分析。结果哮喘组和肥胖组Rn值显著高于正常对照组,肥胖型哮喘组Rn值高于其余各组,干预组Rn显著低于哮喘组和肥胖型哮喘组(P均<0.01),而干预组Rn与正常组比较,差异无统计学意义(P>0.05)。经乙酰甲胆碱激发后,哮喘组和肥胖组小鼠Rn值上升幅度显著高于正常对照组(P<0.01),肥胖型哮喘组Rn值上升幅度高于其余各组,干预组小鼠较哮喘组、肥胖组和肥胖型哮喘组小鼠比较,Rn值上升幅度显著降低(P均<0.01);而干预组小鼠Rn值的上升幅度与正常对照组比较,差异无统计学意义(P>0.05)。结论雷公藤红素显著减轻肥胖型哮喘小鼠呼吸气道阻力,改善了其AHR。

Objective To study the effect of celastrol use on the airway hyperresponsiveness of obese asthma mice. Methods Thirty male C57BL/6 mice were randomly allocated to 5 groups. Mice in obese asthma group and eelastrol group were fed with a high fat diet （HFD） for 16 weeks. On days 1 and 13 from the week 13, mice in the two groups were intraperitoneal injected with ovalbumin for a mouse asthma model, then the mice were nebulized with ovalbumin for 7 consecutive days from day 25 to 31. Mice in celastrol group were garaged celastrol 10mg/kg 30min before being exposed to aerosolized ovalbumin. Mice in asthma group were fed with a normal diet, sensitized and challenged by OVA. Mice in obesity group were fed with HFD, sensitized and challenged by NS. Mice in normal weight group, as a control, were fed with a normal diet, sensitized and challenged by NS. Mouse spirometer was used to detect airway responsiveness. Results The resistence of airway（Rn） in obese group and asthma group were significantly higher than normal weight group. Obese asthma group was the highest, and celatrol group was significantly lower than asthma group and obese asthma group（ all P 〈 0.01 ）. There were no differences between celastrol group and normal weight group （ P 〉 0.05）. With the challenge of methacholine, Rn was growing rapidly in asthma group, obese group and obese asthma group, significantly faster than normal weight group and celastrol group （ all P 〈 0.01 ）. There were no differences between celastrol group and normal weight group （P 〉 0.05）. Conclusion These results suggest that oral administration of celastrol alleviated airway hyperresponsiveness, may be used as a therapeutic agent for obese asthma.