摘要目的 观察青蒿琥酯对哮喘小鼠气道反应性和气道炎症的影响.方法 30只6～8周龄雌性BALB/c小鼠按随机数字表法分为对照组、哮喘组和青蒿琥酯组.哮喘组和青蒿琥酯组分别在第0、14天给予卵白蛋白(OVA)20 μg与氢氧化铝2 mg混悬液0.2 ml腹腔注射致敏,第21～28天给予溶于无菌磷酸盐(PBS)缓冲液的1％OVA 10 ml行雾化激发30 min,对照组第0、14天用氢氧化铝2mg混悬液0.2 ml腹腔注射致敏,第21～28天无菌PBS 10 ml雾化激发.每次激发前青蒿琥酯组腹腔注射青蒿琥酯0.2 ml,对照组和哮喘组以等量生理盐水代替,末次激发24h后处理小鼠,气道插管法测定小鼠的气道反应性,观察气道阻力和顺应性变化;支气管肺泡灌洗液(BALF)行细胞学分类,观察左肺组织的病理变化并评分.结果 三组小鼠气道阻力均随乙酰甲胆碱(Ach)浓度的增加而增加,肺顺应性随Ach浓度的增加而下降,相同浓度下三组小鼠整体的气道阻力和肺顺应性不同(P＜0.05);青蒿琥酯组在Ach 6.25、12.5、25、50、100 mg/ml浓度下的气道阻力值低于相同浓度下的哮喘组[(1.01±0.48)比(1.30±0.22)、(1.06±0.44)比(1.70±0.31)、(1.30±0.64)比(2.66±0.79)、(1.82±0.55)比(3.38±1.35)、(2.49±0.85)比(4.07±1.34) cmHl20·s-1·ml-1(1 cmH20=0.098 kPa);t=3.862、7.376、9.113、7.051、6.685,均P＜0.05],在Ach 3.125、6.25、12.5、25、50、100 mg/ml浓度下的肺顺应性下降程度低于相同浓度下的哮喘组[(3.89±0.55)×10-2比(3.07±0.63)×10-2、(3.61±0.52)×10-2比(3.04±0.58)×10-2、(3.48±0.38)×10-2比(2.78±0.57)×10-2、(3.09±0.52)×10-2比(1.73±0.62)×10-2、(2.32±0.60)×10-2比(1.29±0.54)×10-2、(1.87±0.59)×10-2比(1.15±0.44)×10-2ml/cmH2O;t=-6.295、-4.921、-6.533、-11.135、-8.148、-6.319,均P＜0.05].BALF中青蒿琥酯组嗜酸性粒细胞的比例明显低于哮喘组[(16.63±8.58)％比(40.44±12.94)％;t=4.336,P＜0.05].哮喘组肺组织支气管和血管周围明显炎症细胞浸润,支气管黏膜上皮水肿、变性,青蒿琥酯组能够减轻支气管和血管周围的炎症细胞浸润,黏液分泌减少.结论 青蒿琥酯能够改善哮喘小鼠的气道高反应性和气道炎症,对哮喘有一定的治疗作用.

abstractsObjective To observe the effects of artesunate on airway responsiveness and airway inflammation in asthmatic mice.Methods Thirty female BALB/c mice aged 6-8 weeks were randomly divided into control group,asthma group and artesunate group.In the asthma group and the artesunate group,the mice were sensitized by intraperitoneal injection of 20 μg of ovalbumin (OVA) and 0.2 ml of aluminum hydroxide suspension (2 mg) on day 0 and 14,respectively,and 1％ OVA 10 ml dissolved in sterile phosphate (PBS) buffer was aerosolized for 30min from the 21st to 28th day.The control group was sensitized with 0.2 ml of 2 mg suspension of aluminum hydroxide on day 0 and 14,and aerosolized by 10 ml of sterile PBS from the 21st to 28th day.Before the challenge,the artesunate group was intraperitoneally injected with 0.2 ml of artesunate.Artesunate was replaced with the same amount of normal saline in the control group and the asthma group.The mice were treated after 24 hours of last stimulation.The airway responsiveness of mice was measured by airway intubation and the changes of airway resistance and compliance were observed.Bronchoalveolar lavage fluid (BALF) was classified by cytology,and pathological changes of left lung tissue were observed and scored.Results The airway resistance of the three groups increased and the lung compliance decreased with the increase of methacholine (Ach) concentration.The airway resistance and lung compliance of the three groups were different under the same concentration (P＜ 0.05).The airway resistance of the artesunate group at Ach 6.25,12.5,25,50,100 mg/ml was lower than that of the asthma group at the same concentration [(1.01±0.48) vs (1.30±0.22),(1.06±0.44) vs (1.70±0.31),(1.30±0.64) vs (2.66±0.79),(1.82±0.55) vs (3.38± 1.35),(2.49±0.85) vs (4.07±1.34) cmH2O· s-1· ml-1 (1 cmH2O=0.098 kPa);t=3.862,7.376,9.113,7.051,6.685,all P＜0.05];the degree of lung compliance decrease at the concentration of Ach 3.125,6.25,12.5,25,50,100 mg/ml was lower than that of the asthma group at the same concentration [(3.89±0.55)×10-2 vs (3.07±0.63)×10-2,(3.61±0.52)×10-2 vs (3.04±0.58)× 10-2,(3.48±0.38)× 10-2 vs (2.78±0.57)× 10-2,(3.09±0.52)× 10-2 vs (1.73±0.62)× 10-2,(2.32±0.60)× 10-2 vs (1.29±0.54)× 10-2,(1.87±0.59)× 10-2 vs (1.15±0.44)× 10-2 ml/cmH2O;t=-6.295,-4.921,-6.533,-11.135,-8.48,-6.319,all P＜0.05].The proportion of eosinophils in artesunate group in BALF was significantly lower than that in asthma group [(16.63±8.58)％ vs (40.44±12.94)％;t=4.336,P＜0.05].In the asthma group,the inflammatory cells infiltration of the bronchi and the perivascular area,the bronchial epithelial edema and degeneration can be observed,and the artesunate could reduce the infiltration of inflammatory cells around the bronchus and blood vessels,and the mucus secretion was also reduced in the artesunate group.Conclusion Artesunate can improve airway hyperresponsiveness and airway inflammation in asthmatic mice and has a certain therapeutic effect on asthma.