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异丙酚对哮喘小鼠气道保护作用的炎症机制研究

发布时间:2018-09-11 14:52
【摘要】:目的观察腹腔注射不同剂量异丙酚对哮喘小鼠气道高反应性和气道炎症的调节作用。 方法健康雌性BALB/c小鼠100只,6-8周龄,体重18~20g,随机分为5组(n=20):对照组(腹腔注射生理盐水,C组)、哮喘组(腹腔注射生理盐水,A组)、哮喘+小剂量异丙酚组(腹腔注射50mg/kg异丙酚,A+LP组)、哮喘+中等剂量异丙酚组(腹腔注射100mg/kg异丙酚,A+MP组)、哮喘+大剂量异丙酚组(腹腔注射150mg/kg异丙酚,A+HP组)。A组、A+LP组、A+MP组、A+HP组使用卵清蛋白(ovalbumin, OVA)建立过敏性哮喘小鼠模型,C组使用生理盐水作为对照组。每组再随机分成两小组(每小组n=10),一组于模型建立成功后24小时,进行肺功能检测和取肺组织HE染色,比较各组小鼠气道反应性和肺组织的病理组织学评分;另一组于模型建立成功后24小时,给予致死剂量戊巴比妥钠处死,进行心脏取血及支气管肺泡灌洗,以酶联免疫吸附实验方法(enzyme-linked immunosorbent assay, ELISA)检测血清OVA特异性免疫球蛋白E(immunoglobulin E, IgE)和支气管肺泡灌洗液中特征性细胞因子白介素-4(interleukin-4, IL-4)、 IL-5、干扰素-γ (interferon-y, IFN-γ)。 结果腹腔注射小剂量和中等剂量的异丙酚(A+LP组和A+MP组)可明显地抑制哮喘小鼠的气道高反应性,而腹腔注射大剂量的异丙酚(A+HP组)未能明显地抑制哮喘小鼠的气道高反应性。不同剂量的异丙酚干预(A+LP组、A+MP组和A+HP组)可使哮喘小鼠肺组织中嗜酸性粒细胞浸润程度显著减轻(P0.05),支气管肺泡灌洗液中IL-4、IL-5和血清中OVA特异性IgE水平显著降低(P0.05),支气管肺泡灌洗液中IFN-γ/IL-4比值显著升高(P0.05)。 结论异丙酚通过减轻哮喘小鼠肺部嗜酸性粒细胞浸润程度,降低血清中OVA特异性IgE水平,降低支气管肺泡灌洗液中IL-4.IL-5水平和上调IFN-y/IL-4比值,有效降低哮喘小鼠的气道阻力,最终发挥气道保护作用。
[Abstract]:Objective to observe the effects of intraperitoneal injection of propofol on airway hyperresponsiveness and airway inflammation in asthmatic mice. Methods 100 healthy female BALB/c mice were aged 6-8 weeks. Weight 1820 g, randomly divided into 5 groups: control group (intraperitoneal injection of normal saline group C), asthma group (intraperitoneal injection of normal saline group A), asthma group (intraperitoneal injection of 50mg/kg propofol group A LP), asthma group (intraperitoneal injection of propofol A LP) Establishment of allergic Asthma mice by ovalbumin (ovalbumin, OVA) in the same dose propofol group (intraperitoneal injection of 100mg/kg propofol A MP group), asthma high-dose propofol group (intraperitoneal injection of 150mg/kg propofol A HP group) .A LP group A MP group A HP group using ovalbumin (ovalbumin, OVA) Model group C was treated with normal saline as control group. Each group was randomly divided into two groups (n = 10 each). The lung function was measured and lung tissue HE staining was performed 24 hours after the establishment of the model. The airway reactivity and the histopathological score of lung tissue in each group were compared. The other group was given lethal dose of pentobarbital sodium 24 hours after the establishment of the model, and the blood was taken from the heart and bronchoalveolar lavage. Enzyme linked immunosorbent assay (enzyme-linked immunosorbent assay, ELISA) was used to detect serum OVA specific immunoglobulin E (immunoglobulin E, IgE), interleukin-4 (interleukin-4, IL-4) and IL-5, interferon- 纬 (interferon-y, IFN- 纬) in bronchoalveolar lavage fluid (BALF). Results Intraperitoneal injection of propofol (A LP and A MP significantly inhibited airway hyperresponsiveness in asthmatic mice. However, intraperitoneal injection of propofol (A HP did not significantly inhibit airway hyperresponsiveness in asthmatic mice. Different doses of propofol in (A LP group (A MP group and A HP group) significantly reduced the infiltration of eosinophils in lung tissue of asthmatic mice (P0.05), and significantly decreased the levels of IL-4,IL-5 in bronchoalveolar lavage fluid and OVA specific IgE in serum. Low (P0.05), the ratio of IFN- 纬 / IL-4 in bronchoalveolar lavage fluid increased significantly (P0.05). Conclusion propofol can effectively reduce the airway resistance of asthmatic mice by reducing the infiltration of eosinophil in lung, reducing the level of OVA specific IgE in serum, decreasing the level of IL-4.IL-5 in bronchoalveolar lavage fluid and upregulating the ratio of IFN-y/IL-4. Finally give play to the role of airway protection.
【学位授予单位】:北京协和医学院
【学位级别】:硕士
【学位授予年份】:2013
【分类号】:R614;R562.25

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