本文選題：哮喘　切入點(diǎn)：單克隆抗體　出處：《第三軍醫(yī)大學(xué)學(xué)報(bào)》2014年12期

【摘要】：目的研究趨化因子配體20(CC chemokine ligand 20,CCL20)在哮喘小鼠肺組織內(nèi)的表達(dá),觀察抗小鼠CCL20單克隆抗體對(duì)哮喘小鼠肺部炎癥和氣道高反應(yīng)的抑制作用。方法 6~8周齡雌性BALB/c小鼠按隨機(jī)數(shù)字表法分為4組:哮喘組、正常對(duì)照組、CCL20單克隆抗體治療組(單抗組)和治療對(duì)照組,每組8只。哮喘組予卵蛋白(ovalbumin,OVA)致敏和激發(fā)建立哮喘小鼠模型,單抗組和治療對(duì)照組致敏和激發(fā)同哮喘組,但自第1次激發(fā)起,霧化前1 h分別腹腔注射給予抗小鼠CCL20單克隆抗體或磷酸鹽緩沖溶液(PBS),連續(xù)5 d。正常對(duì)照組用PBS代替OVA進(jìn)行致敏和激發(fā)。末次激發(fā)后24 h用無創(chuàng)肺功能體描儀行小鼠氣道反應(yīng)性檢測(cè),HE染色觀察肺組織病理炎癥及評(píng)分,免疫組化及圖像分析和實(shí)時(shí)熒光定量PCR分別測(cè)定小鼠肺組織CCL20的蛋白含量和基因表達(dá)水平。結(jié)果哮喘組小鼠肺組織炎癥病理評(píng)分、氣道高反應(yīng)、肺組織CCL20 mRNA相對(duì)表達(dá)量及免疫組化CCL20平均光密度值均顯著高于正常對(duì)照組。與哮喘組相比,單抗組小鼠肺部細(xì)胞浸潤(rùn)減輕(P0.05),肺功能(霧化乙酰甲膽堿濃度為25~50 mg/mL時(shí))Penh降低(P0.05),肺組織CCL20平均光密度值顯著降低(P0.01),而CCL20 mRNA表達(dá)無影響。結(jié)論 CCL20單克隆抗體可改善OVA誘發(fā)的小鼠哮喘炎癥和氣道高反應(yīng),其抑制作用可能與抗鼠CCL20單抗阻斷部分CCL20活性有關(guān)。
[Abstract]:Objective to investigate the expression of chemokine ligand 20(CC chemokine ligand 20 (CCL20) in lung tissue of asthmatic mice and to observe the inhibitory effect of anti CCL20 monoclonal antibody on pulmonary inflammation and airway hyperresponsiveness in asthmatic mice.Methods female BALB/c mice aged 6 weeks and 8 weeks were randomly divided into four groups: asthma group, normal control group, CCL20 monoclonal antibody treatment group and treatment control group, with 8 mice in each group.Asthma group was sensitized with ovalbumin OVA) and stimulated to establish asthma model. The monoclonal antibody group and treatment control group were sensitized and stimulated with the same asthma group, but since the first stimulation,The mice were injected intraperitoneally with CCL20 monoclonal antibody or phosphate buffer solution 1 h before atomization for 5 days.The normal control group was sensitized and stimulated by PBS instead of OVA.24 hours after the last challenge, the lung tissue inflammation and score were observed by using noninvasive pulmonary function scintigraphy to detect the airway reactivity of mice and to observe the pathological inflammation of lung tissue by HE staining.Immunohistochemistry, image analysis and real-time fluorescence quantitative PCR were used to detect the protein content and gene expression of CCL20 in lung tissue of mice.Results the inflammatory pathological score, airway hyperresponsiveness, the relative expression of CCL20 mRNA and the average optical density of CCL20 in lung tissue of asthmatic mice were significantly higher than those of normal control group.Compared with the asthmatic group, the lung cell infiltration in the monoclonal antibody group decreased P0.05A, and the lung function (the concentration of nebulized methacholine was 25 mg/mL, Penh decreased P0.05N, the mean optical density of CCL20 in lung tissue decreased significantly, but the expression of CCL20 mRNA was not affected.Conclusion CCL20 monoclonal antibody can improve asthmatic inflammation and airway hyperresponsiveness induced by OVA in mice, and its inhibitory effect may be related to the blocking of partial CCL20 activity by anti-mouse CCL20 monoclonal antibody.
【作者單位】： 重慶醫(yī)科大學(xué)附屬兒童醫(yī)院兒童發(fā)育疾病研究省部共建教育部重點(diǎn)實(shí)驗(yàn)室;重慶醫(yī)科大學(xué)附屬兒童醫(yī)院呼吸中心;
【分類號(hào)】：R562.25

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