【摘要】 目的探讨12-烷基化壳聚糖纳米粒(12-ACSs)包裹的反义内皮素转换酶(ECE)核酸表达质粒对哮喘模型小鼠气道高反应性的影响。方法将40只小鼠按完全随机设计原则分为4组,每组10只。AS组予OVA致敏激发气道炎症并只给予生理盐水干预组;N组仅维予生理盐水致敏,激发并治疗;NM组于OVA致敏激发并给予包裹反义ECE核酸的12-ACSs;DNA组以OVA致敏激发并给予裸反义ECE核酸。3组在致敏后于首次激发前24小时分别通过气道灌注包裹反义ECE核酸的12-ACSs100μl、0.9%生理盐水100μl和反义ECE核酸5μg加0.9%生理盐水(总量100μl),N组用等体积0.9%生理盐水处理。末次激发后检测进行支气管肺泡灌洗,计算支气管肺泡灌洗液中细胞总数、分类计数,肺组织病理切片,观察病理变化。采用整体体积描记法检测小鼠气道反应性,ELISA法检测脾细胞培养上清液白细胞介素(IL)-4、和内皮素1(ET-1)水平。结果 NM组小鼠支气管肺泡灌洗液细胞总数、分类计数明显低于As组和DNA组(均P<0.01),肺组织的病理损害明显减轻。As、NM、DNA组较N组小鼠气道气道反应性明显增高,而NM组气道阻力较As及DNA组明显降低。脾细胞培养上清液N组ET与IL-4水平均明显低于其余3组,而NM组ET与IL-4水平则明显低于As组和DNA组(均P<0.001)。结论气道内给予包裹反义ECE核酸表达质粒的12-ACSs纳米粒治疗,可以减少ET的合成,从而抑制气道高反应性。更多还原

【Abstract】 To explore the effect of 12-ACSs on bronchial hyper-responsiveness in asthma model mice.Forty Balb/c mice were randomly divided into four groups:N,NM,AS and DNA groups,10 animals in each.In the NM,AS and DNA groups the mice were sensitized with OVA.The asthmatic mice in the three groups were peritoneal injected with 12-ACSs/antisense-ECE plasmid,saline,and DNA antisense-ECE plasmid,respectively.In the N group,the animals were injected with saline.Bronchoalveolar lavage was accomplished in mice to calculate the total cell count and the differential count in the lavage fluid.The levels of interleukin(IL)-4 and endothelin(ET)-1 in the supernatant of spleen cell culture were detected by using ELISA.Lung tissues were embedded,sliced and hematoxylin-eosin stained for histopathologic examination.Airway hyper-reactivity to methacholine was evaluated by whole-body plethysmography.The mice in the NM group showed a lower level of cell count than that in the AS and DNA groups.Compared with the N group,the lung tissues taken from the mice in the AS and DNA groups displayed allergic inflammation with Eos infiltration.In contrast,the pulmonary inflammation was decreased significantly in the NM group.The levels of ET were down-regulated in the NM group compared to the AS and DNA groups(P<0.01).The levels of IL-4 were also down-regulated in the NM group compared to the AS and DNA groups.Airway hyper-reactivity of mice in the NM,AS and DNA groups were significantly increased compared with the N group and airway hyper-reactivity of AS and DNA group were significantly increased compared with the NM groups.The 12-ACSs have the capability of down-regulating the synthesis of ET-1 and can release the airway hyper-reactivity.更多还原