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異丙酚對(duì)哮喘小鼠氣道保護(hù)作用的炎癥機(jī)制研究

發(fā)布時(shí)間:2018-09-11 14:52
【摘要】:目的觀察腹腔注射不同劑量異丙酚對(duì)哮喘小鼠氣道高反應(yīng)性和氣道炎癥的調(diào)節(jié)作用。 方法健康雌性BALB/c小鼠100只,6-8周齡,體重18~20g,隨機(jī)分為5組(n=20):對(duì)照組(腹腔注射生理鹽水,C組)、哮喘組(腹腔注射生理鹽水,A組)、哮喘+小劑量異丙酚組(腹腔注射50mg/kg異丙酚,A+LP組)、哮喘+中等劑量異丙酚組(腹腔注射100mg/kg異丙酚,A+MP組)、哮喘+大劑量異丙酚組(腹腔注射150mg/kg異丙酚,A+HP組)。A組、A+LP組、A+MP組、A+HP組使用卵清蛋白(ovalbumin, OVA)建立過(guò)敏性哮喘小鼠模型,C組使用生理鹽水作為對(duì)照組。每組再隨機(jī)分成兩小組(每小組n=10),一組于模型建立成功后24小時(shí),進(jìn)行肺功能檢測(cè)和取肺組織HE染色,比較各組小鼠氣道反應(yīng)性和肺組織的病理組織學(xué)評(píng)分;另一組于模型建立成功后24小時(shí),給予致死劑量戊巴比妥鈉處死,進(jìn)行心臟取血及支氣管肺泡灌洗,以酶聯(lián)免疫吸附實(shí)驗(yàn)方法(enzyme-linked immunosorbent assay, ELISA)檢測(cè)血清OVA特異性免疫球蛋白E(immunoglobulin E, IgE)和支氣管肺泡灌洗液中特征性細(xì)胞因子白介素-4(interleukin-4, IL-4)、 IL-5、干擾素-γ (interferon-y, IFN-γ)。 結(jié)果腹腔注射小劑量和中等劑量的異丙酚(A+LP組和A+MP組)可明顯地抑制哮喘小鼠的氣道高反應(yīng)性,而腹腔注射大劑量的異丙酚(A+HP組)未能明顯地抑制哮喘小鼠的氣道高反應(yīng)性。不同劑量的異丙酚干預(yù)(A+LP組、A+MP組和A+HP組)可使哮喘小鼠肺組織中嗜酸性粒細(xì)胞浸潤(rùn)程度顯著減輕(P0.05),支氣管肺泡灌洗液中IL-4、IL-5和血清中OVA特異性IgE水平顯著降低(P0.05),支氣管肺泡灌洗液中IFN-γ/IL-4比值顯著升高(P0.05)。 結(jié)論異丙酚通過(guò)減輕哮喘小鼠肺部嗜酸性粒細(xì)胞浸潤(rùn)程度,降低血清中OVA特異性IgE水平,降低支氣管肺泡灌洗液中IL-4.IL-5水平和上調(diào)IFN-y/IL-4比值,有效降低哮喘小鼠的氣道阻力,最終發(fā)揮氣道保護(hù)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- 緯 (interferon-y, IFN- 緯) 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- 緯 / 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.
【學(xué)位授予單位】:北京協(xié)和醫(yī)學(xué)院
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2013
【分類號(hào)】:R614;R562.25

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