地塞米松对中性粒细胞性哮喘模型小鼠气道炎症的影响
地塞米松对中性粒细胞性哮喘模型小鼠气道炎症的影响发表时间：2015-07-03T13:39:03.633Z 来源：《医药前沿》2015年第8期供稿作者：詹文杰[导读] 哮喘是最常见的慢性呼吸道疾病，其本质是多种细胞及细胞组分共同参与的慢性气道炎症。
詹文杰(广西医科大学广西南宁 530021)【摘要】目的：观察地塞米松对中性粒细胞性哮喘（neutrophilic asthma，NA）模型小鼠气道炎症的影响。
方法：C57BL雌性小鼠随机分成NA组、NA地塞米松干预（neutrophilic asthma treating with dexamethasone，NAD）组和正常（NC）组，每组8只。
NA、NAD组予卵蛋白、脂多糖致敏并卵蛋白激发；NAD组激发前腹腔注射地塞米松；NC组不做处理。
小鼠肺功能仪检测气道阻力，以阻力倍增值评价气道反应性；检测支气管肺泡灌洗液（bronchoalveolar lavage fluid，BALF）有核细胞浓度及分类比例；流式细胞术检测脾脏Th17细胞及ki-67+Th17细胞比例；ELISA检测BALF IL-17浓度。
结果（1）NA组气道阻力倍增值显著高于NC组（P<0.05）。
（2）NAD组BALF有核细胞浓度、NEU%、EOS%均显著低于NA组，但仍高于NC组（均P<0.05）。
（3）NAD组脾脏Th17细胞比例显著低于NA组，但仍高于NC 组（均P<0.05）；NA、NAD组脾脏ki-67+Th17细胞比例均显著高于NC组（均P<0.05），但NA、NAD组间差异无统计学意义。
（4）NAD 组BALF IL-17浓度显著低于NA组，但仍高于NC组（均P<0.05）。
结论：地塞米松可能通过抑制Th17细胞及IL-17表达，减轻NA模型小鼠气道炎症；Th17细胞增殖功能增强且不受地塞米松影响可能与气道炎症持续存在有关。
【关键词】哮喘；中性粒细胞；气道炎症；地塞米松【中图分类号】R965 【文献标识码】A 【文章编号】2095-1752（2015）08-0345-03 Effect of dexamethasone on airway inflamation in the mouse model of neutrophilic asthma【Abstract】Objective To observe the effect of dexamethasone on airway inflammation in the mouse model of Neutrophilic Asthma.Methods Female C57BL mice were randomly divided into NA, NAD and NC group.NA、NAD mice were sensitized by ovalbumin OVA and LPS and challenged by OVA. NAD mice were treated with dexamethasone at beginning of each challenge.NC mice without treatment.Airway resistance were measured and fold increase were caculated as an assessment for AHR.Total white blood cell concentration and classification of proportion were determined in the BALF.Percentages of Th17 cells and Ki-67+Th17 cells in the spleen were determined by FCM.BALF IL-17 concentration were determined by ELISA. Results (1) Fold increase of airway resistance in the NA group were higher than that of the NC group (each P<0.05).（2）BALF total cell count, neutrophil and eosinophil percentages in the NAD group were lower than that of the NA group (each P<0.05), but were higher than that of the NC group(each P<0.05). (3) Th17 cell percentages in the spleen of the NAD group were lower than that of the NA group, but were higher than that of the NC group(each P<0.05). Ki-67+Th17 cells percentage in the spleen of the NA and NAD group were higher than that of the NC group(each P<0.05);Hoever,no difference were found in the NA group compared with that of the NAD group（4）BALF IL-17 concentration in the NAD group were lower than that of the NA group, but were higher than that of the NC group(each P<0.05). Conclusions Airway inflammation in the mouse model of NA were improved by dexamethasone via its inhibition on the exspression of Th17 cells.The enhanced function of Th17 cells proliferation not influenced by dexamethasone，may be responsible for the persistence of the inflammation.【Keywords】Asthma; Neutrophil;Airway inflammation; Dexamethasone哮喘是最常见的慢性呼吸道疾病，其本质是多种细胞及细胞组分共同参与的慢性气道炎症。
气道反应性增高、可逆性气流受限、气道黏液高分泌及不可逆性气道重塑是其特点。
糖皮质激素抗炎作用良好，被广泛用于治疗哮喘。
Schwartz等首先发现一组激素治疗不佳的患者，并率先提出哮喘“激素抵抗”的概念 [1]。
研究表明，哮喘存在嗜酸细胞性哮喘和非嗜酸细胞性哮喘两个亚型，非嗜酸细胞性哮喘中有超过半数为中性粒细胞性哮喘，表现为中性粒细胞浸润为主的气道炎症 [2]。
中性粒细胞性气道炎症被认为与哮喘发作、重症哮喘及激素抵抗均有关 [3-5]，其机制仍在研究。
Th17细胞是能够分泌IL-17的辅助性T细胞亚群，IL-17可诱导多种靶细胞分泌相关细胞因子，趋化中性粒细胞局部浸润 [6]。
Th17细胞介导中性粒细胞局部浸润的作用可能与哮喘中性粒细胞性气道炎症的发生有关[7]。
Wilson等发现，气道炎症以中性粒细胞浸润为主的模型小鼠，存在着强烈的Th17细胞反应，提示Th17细胞可能介导该模型小鼠中性粒细胞性气道炎症的发生[8]。
McKinley等将Th17细胞灌输给小鼠并予OVA激发，小鼠气道中性粒细胞浸润明显，且不受地塞米松抑制，提示Th17细胞可能不仅介导中性粒细胞性气道炎症，还可能与激素抵抗有关[9]。
基于上述研究情况，本研究参照刘晓微等方法[10]，建立中性粒细胞性哮喘小鼠模型，并予地塞米松作用，观察地塞米松对模型小鼠气道炎症的影响，并探讨Th17细胞的作用。
1.材料与方法1.1 实验对象及分组SPF级C57BL雌性小鼠，随机分入NA组、NAD组和NC组，每组8只。
1.2 主要试剂和器材脂多糖、卵蛋白，地塞米松磷酸钠注射液，Diff-Quik染液，FACS Calibur型流式细胞仪及抗体，ELISA 试剂盒，光学显微镜，细胞甩片机，雾化泵及喷雾器，小鼠肺功能仪等。
1.3 中性粒细胞性哮喘小鼠模型制备NA、NAD组小鼠均于第0、6、13天经气道滴入100μg 卵蛋白及0.1μg脂多糖致敏，共3次；于第21、22、23天，均雾化吸入1% 卵蛋白激发，每天1次，每次60min；NAD组小鼠每次激发开始前30min按1mg/kg经腹腔注射地塞米松。
1.4 标本收集及指标检测小鼠均于最后一次雾化结束后第24小时收集标本或检测指标。
1.4.1气道阻力检测小鼠予50mg/kg 1％戊巴比妥钠腹腔注射麻醉，气管插管，小鼠肺功能仪上依次雾化10ul倍增浓度乙酰甲胆碱（methacholine，Mch）并检测总气道阻力，以上机开始时的平稳阻力为基础阻力值R(baseline)，以吸入乙酰甲胆碱后的最高值为各浓度激发时的阻力值R(response)，以气道阻力倍增值（=[R(response)- R(baseline)]/R(baseline)）评价气道反应性。
1.4.2 BALF收集及检测静脉留置针气管插管，0.5ml冷PBS反复灌洗支气管肺泡两次，回收BALF（回收率达80%）。
血球计数板上检测有核细胞浓度，适量BALF甩片后Diff-Quik染色，光镜下分类计数并计算分类比例。
1.4.3流式细胞术检测脾脏Th17细胞及ki-67+Th17细胞的比例取脾脏，制备脾脏单细胞悬液,PMA、离子霉素于培养箱（5%CO2，37℃）孵育刺激5小时,再经①细胞外染PerCP-Cy?5.5 Rat Anti-Mouse CD4、APC Rat Anti-Mouse CD8，②Fix/Perm Buffer细胞破膜，③细胞内染PE Rat Anti-Mouse IL-17A、FITC Mouse Anti-Human Ki-67，④1%多聚甲醛固定，流式细胞仪上机检测。
注：与NC组比较aP<0.05；与NAD组比较bP<0.05。
3.讨论哮喘是多种细胞及细胞组分共同参与的慢性气道炎症性疾病，气道反应性增高、可逆性气流受限、气道黏液高分泌和不可逆性气道重塑是其特点。
地塞米松对哮喘小鼠支气管肺泡灌洗液中IL-25和IFN-γ的影响
地塞米松对哮喘小鼠支气管肺泡灌洗液中IL-25和IFN-γ的影响陆韦;王蕾;谯明;王玉;江吉富;吴中明【摘要】Objective To investigate the mechanism of therapeutic action of dexamethasone on asthmatic mice by detecting the levels of IL-25 and IFN-γ in bronchoalveolar lavage fluid (BALF). Methods Balb/c mice with SPF grade were randomly divided into normal control group, asthma group and dexamethasone group. Asthma group and dexamethasone group were sensitized and challenged with ovalbumin ( OVA) . Dexamethasone group was intraperitoneally injected with dexamethasone one hour before challenging. The mice were executed 24 hours after the last challenge, and the HE stained pathological sections of the right lung were made. Pathological sections of lung were observed. BALF in the left lung was also collected. The total white blood cell count and absolute eosinophile ( EOS) count were observed, and the percentage of EOS was calculated. The levels of IL-25 and IFN-γwere measured with ELISA, and correlation analyses were made. Results The counts of total white blood cell and EOS, and the percentage of EOS were significantly higher in the asthma group than in the normal control group and dexamethasone group (P<0. 05). No differences were found between the normal control group and dexamethasone group. The IL-25 level was higher in the asthma group than in the normal control group and dexamethasone group (P<0. 05), and its level in the dexamethasone group was also higher than that in thenormal control group. The IFN-γlevel was lower in the asthma group thanin the normal control group and dexamethasone group (P<0. 05), while there was no significant difference between the normal control group and dexamethasone group. IL-25 was negatively correlated with IFN-γin each group. Conclusion Part of the mechanisms of dexamethasone acting on asthma are related to its inhibition on the pulmonary inflammation and promotion on the expression of IFN-γ, and possible inhibition of IL-25 expression.%目的通过检测支气管肺泡灌洗液(BALF)中白细胞介素-25(IL-25)和γ-干扰素(IFN-γ)的水平,探讨地塞米松对小鼠支气管哮喘的治疗作用机制。
地塞米松对呼吸道合胞病毒感染哮喘加重小鼠气道TSLP分泌及炎症的影响
及 气 道 炎 症 的影 响 。 方 法 ： 性 Ｂ Ｌ ／ 小 鼠 ３ 雌 Ａ Ｂｅ ２只 ， 机 分 成 ４组 ， 别 为 磷 酸盐 缓 冲 液 （Ｂ ） 照 组 、 卵 白蛋 白 （ Ｖ 组 、 随 分 ＰＳ对 鸡 Ｏ Ａ）
Ｏ Ａ Ｒ Ｖ组 、 Ｖ ／ Ｓ ／ Ｅ Ｖ／ Ｓ Ｏ Ａ Ｒ Ｖ Ｄ Ｘ组 ； 应用 Ｏ Ａ腹 腔注射致敏 、 Ｖ Ｖ Ｏ Ａ气道雾化结合 Ｒ Ｖ滴鼻激发哮喘 ， Ｓ 地塞米松 ｌ ｓｋ 肌 肉注射 ； ｍ ／ｇ
ｄｖｄ ｄ ｉｔ ｕ ｒｕ ｓ Ｐ Ｓ ｃ ｎｒｌｇｏ ｐ， ＶＡ ｇ ｏ ｐ ａ ｄＯＶ ／ Ｓ ｇｏ ｐ ａ ｄ Ｏ Ａ ＲＳ ／ Ｅ ｒｕ Ｍｉｅ ｗ ｒ ｅ ｓ ｉ ｄ ｂ Ａ ａ ｄ ｉｉｅ ｎｏ ｆ ｒｇ ｏ ｐ ： Ｂ ｏ ｔ ｒｕ Ｏ ｒｕ ， ｎ Ａ Ｒ Ｖ ｒｕ ， Ｖ ／ Ｖ Ｄ Ｘ ｇｏ ｐ． ｃ ｅｅ ｓｎ ｉ ｚ ｙＯＶ ｎ ｏ ｏ ｎ ｔｅ ｓｉ ｌｔ ｔ ｅ ｕｉ ｄ Ｏ ｔ ｍｕａｅ ｗｉ ｎ ｂ ｌ ｅ ＶＡ． Ｓ ａ ｎ ｃ ａｅ ｔ ｒ ｅ ｎ ａ ｃ ｖｔ ｄ １ｍｇ ｋ ｆＤＥ ｗ ｓ ｉｔ ｍｕ ｃ ａ ｌ ａ ｍｉｉｔｒｄ Ｂ ＸＣ ｄ ｈ ｚ Ｒ Ｖ ｗ ｓ ｉｏ ｕ ｔｄ ｉ ｏｍｕ ｉ ａ ｌ ａ ｉ ａ ／ ｇ ｏ Ｘ ａ ｎｒ ｓ ｕ ｒ ｄ ｎ ｓ ｅ ． Ｕ Ｏ ｌ ｎ ｎ ｓ ｙｎ ａ ｌ ｙ ｅ ｎ ｎｎ ａ ｉ ｔ ｎ ｎ ｎ ｔ ｎ ｄ ｔｃｉ ｓｒｍｅ ｔ ａ ｓｄ ｔ ｘ ｍｉ ｅｔｅ ａｒ ａ ｓ ｏ ｓ ｔｅ ｏｉｅ Ｅ ＩＡ ａ ｓ ｄ ｔ ｄ ｔｃ － ｏ ｉｖ ｓｖ ｍｔ ｉｅ ｌ ｇ ｆ ｃ ｏ ｅｅ ｔ ｎ ｉ ｔｕ ｎ ｓ ｅ ｅ ａ ｎ ｉ ｙｒ ｐ ｎ ｅｔ ｍｅ ｈ ｌ ． Ｌ Ｓ ｗ ｕ ｅ ｅｅ ｔ Ｌ ４， ｅ ｒ ｕ ｕ ｉ ｏ ｎ ｗ ｕ ｏ ｈ ｗ ｅ ｏ ａ ｎ ｓ ｏ Ｉ
地塞米松对支气管哮喘模型大鼠气道重建的影响
地塞米松对支气管哮喘模型大鼠气道重建的影响王文建;杨莉【期刊名称】《郑州大学学报（医学版）》【年(卷),期】2007(042)001【摘要】目的:观察地塞米松对哮喘模型大鼠气道重建的影响.方法:24只SD大鼠随机分成哮喘模型组、激素干预组和正常对照组,每组8只,前2组以卵蛋白致敏并长期吸人激发大鼠慢性哮喘模型,正常对照组以生理盐水代替卵蛋白同法处理大鼠.激素干预组每次激发前给予地塞米松0.5 mg/只腹腔注射,哮喘模型组给予等量生理盐水,共4周.最后1次激发后24 h内处死大鼠,取大鼠肺组织行免疫组化测定Ⅰ、Ⅲ型胶原和转化生长因子β1(TGF-β1)的含量,同时测定气道内外径及平滑肌层、网状基底膜的厚度.结果:哮喘模型组气道壁平滑肌和基底膜层厚度及Ⅲ型胶原与TGF-β1含量均高于正常对照组和激素干预组(P均＜0.001),内外径比值低于正常对照组和激素干预组(P＜0.001),而激素干预组和正常对照组以上指标差异无统计学意义;3组间Ⅰ型胶原含量差异无统计学意义(P＞0.05).结论:地塞米松可减少气道壁胶原沉积和平滑肌增生,从而抑制哮喘大鼠气道重建,其机制可能与抑制TGF-β1的表达有关.【总页数】4页(P130-133)【作者】王文建;杨莉【作者单位】无锡儿童医院呼吸科,无锡,214002;东南大学附属中大医院儿科,南京,210009【正文语种】中文【中图分类】R9【相关文献】1.地塞米松对哮喘大鼠气道重建、肥大细胞及IL-10的影响 [J], 刘莉;余可斐;穆敬平;黎瑞红;孟忠吉;赵磊2.转化生长因子β1对不同阶段支气管哮喘模型大鼠气道平滑肌细胞外信号调节激酶通道的影响 [J], 蔺鹏翔;张焕萍3.支气管哮喘模型大鼠气道重建的特征及机制 [J], 许淑云;徐永健;张珍祥;倪望;陈士新4.寒喘舒对支气管哮喘模型小鼠气道重建的影响 [J], 洪滔;贾菠;舒坤;黄秀萍;黄云;袁可望;刘志勇;李守明5.平喘方对支气管哮喘模型小鼠气道重建的影响 [J], 朱慧华;虞坚尔;张晓峰;陈燕萍;庞惠芳;王国华;管宇;吴杰因版权原因，仅展示原文概要，查看原文内容请购买。
地塞米松对急性过敏性哮喘小鼠肺水通道蛋白1的影响
０ ． ０ ５ ） ； （ ２ ） 哮喘组 Ａ Ｑ Ｐ １ ｍＲ Ｎ Ａ（ １ ． ９ ０ ￣ ０ ． ２ ９ ） 和 蛋 白质 （ １ ． ３ １ ￣ ０ ． １ ０ ） 明显高 于对照组（ 尸均 ＜ ０ ． ０ １ ） ， 治 疗 后 表 达 明显
下 降（） 哮喘组肺 组织可见较 弥漫的炎性改变 ， 黏液分 泌增多 ， 血管壁水肿 明显 ， 血 管 周 围
有大 量 的 炎 症 细 胞 渗 出 物 ， 治 疗 组 形 态 学 改 变 明 显减 轻 ； Ａ Ｑ Ｐ １在 气 管 黏 膜 上 皮 、 微血 管内皮上 皮 、 支 气 管 周 围 血管床 、 炎 症 细 胞 呈 阳性 表 达 ， 哮 喘 组 表 达 呈 强 阳性 ， 治疗后 表达 明显减弱 。 【 结 论 】Ａ Ｑ Ｐ １在 急 性 哮 喘 小 鼠
ｗｕ Ｂ ａ ｏ － ｊ ｉ ｎ ｇ ， Ｌ Ｉ Ｗｅ ｎ — ｙ ｉ ， Ｔ Ａ Ｎ Ｗｅ ｉ — ｐ ｉ ｎ ｇ ， ＭＡ Ｉ Ｘ ｉ ａ ｎ — ｄ ｉ ， Ｈ Ｕ Ａ Ｎ Ｇ Ｈｕ ａ — ｒ ｏ ｎ ｇ ， Ｌ Ｉ Ｊ ｉ ｎ ｇ
（ Ｄ ｅ ｐ ａ ｒ ｔ ｍｅ ｎ ｔ ｏ ｆ Ｐ ｅ ｄ ｉ ａ ｔ ｒ ｉ ｃ ｓ ， Ｔ ｈ ｅ Ｓ ｅ ｃ ｏ ｎ ｄ Ａ ｆ ｉ ｌ ｉ ａ ｔ ｅ ｄ Ｈ ｏ ｓ ｐ ｉ ｔ ａ ｌ ， Ｓ Ｕ Ｎ Ｙ ａ ｔ － ｓ ｅ ｎ Ｕ ｎ ｉ ｖ ｅ ｒ ｓ ｉ ｔ ｙ ， Ｇ ｕ ａ ｎ ｇ ｚ ｈ ｏ ｕ ５ １ ０ １ ２ ０ ， Ｃ ｈ ｉ ｎ ａ）
地塞米松对哮喘小鼠气道血管生成及血管内皮生长因子表达的影响
地塞米松对哮喘小鼠气道血管生成及血管内皮生长因子表达的影响姚红卫;吕丽丽【期刊名称】《重庆医学》【年(卷),期】2012(41)36【摘要】Objective To investigate the effects of dexamethsone on airway angiogenesis and transforming vascular endothelial growth factor in chronic asthma mice. Methods The asthmatic model was established by sensitization and challenge with OVA. The mice were randomly divided into three groups ,control group,asthma group and dexamethsone treatment group. After the last chal lenge,eosinophile(EOS) counts and active VEGF level in bronchoalveolar lavage fluid(BALF) were calculated; the pathologic chan ges of bronchi and the lung tissue were evaluated; Anti Factor YUAg antibody was used to detect vessels ,The number of vessels in lamina propria and submucosa of tracheae was counted microscopically; Immuno his to chemistry were used to measure the level of VEGF in the lung tissues of asthmatic mice;the airway wallthickness(WAt/Pbm) and vascular counts were measured by using im age analysis system. Results EOS increased significantly in asthma group compared to that in Dexamethsone group,while between dexamethsone group and control group there was no significantly difference. After repeatedly OVA exposure,the density of vessels and airway wallthickness(WAt/Pbm) and the number of vascular in lung tissues were increased significantly compared with those of control group,which were also positively related with the concentrations of VEGF in lung tissue(P<0.05). Conclusion Dexam ethsone can relieve the allergic inflammation of airway, and ease off airway angiogenesis in asthmatic mice. VEGF was over ex pressed in the asthmatic mice,and may play an important role in airway angiogenesis.%目的探讨地塞米松对哮喘小鼠气道血管生成及血管内皮生长因子(VEGF)表达的影响.方法用鸡卵清蛋白(OVA)致敏和雾化激发建立慢性哮喘小鼠模型,实验分为对照组、哮喘组和地塞米松组.测定支气管肺泡灌洗液(BALF)中白细胞和嗜酸粒细胞(EOS)及活性VEGF表达的变化;行HE染色及VEGF、抗Ⅷ因子免疫组化染色,在显微镜下计数气管黏膜固有层、黏膜下层血管密度,采用医学图像分析软件测定支气管管壁厚度(WAt/Pbm)及肺组织切片中的血管数.结果哮喘组EOS 计数明显升高,气管血管密度、WAt/Pbm及肺组织切片中的血管数明显增加,与VEGF的表达呈正相关.地塞米松组与哮喘组比较炎性反应减轻,气管血管密度、WAt/Pbm及肺组织切片中的血管数减少,VEGF表达减弱,与对照组比较差异有统计学意义(P<0.05).结论 VEGF在哮喘小鼠模型气道及肺组织内过度表达,在气道血管生成过程中可能具有重要作用.早期地塞米松干预可降低哮喘模型的气道炎症,减缓气道血管生成的过程.【总页数】3页(P3854-3856)【作者】姚红卫;吕丽丽【作者单位】江苏省常州市第四人民医院呼吸内科,213001;徐州医学院附属医院老年科,江苏徐州,221008【正文语种】中文【相关文献】1.地塞米松对哮喘小鼠气道炎症反应和STAT6表达的影响 [J], 彭小华;杨远2.血管内皮生长因子受体抑制剂SU5614对哮喘模型小鼠气道炎症的影响 [J], 姜爱英;于仁志;吕玉凤;赵丽丽3.地塞米松对哮喘小鼠气道平滑肌细胞中胸腺活化调节趋化因子表达的影响 [J], 张娟;赵铭山4.地塞米松对哮喘小鼠气道平滑肌细胞增殖及转化生长因子β1表达的影响 [J], 刘平莉;吕丽丽;夏春伟;李若然;姚红卫;朱述阳5.地塞米松对哮喘小鼠中性粒细胞性气道炎症和HMGB1表达的影响 [J], 苏艳新;张明香;刘莎;王婷;谢军;邹文静;阮玲英;罗征秀;符州因版权原因，仅展示原文概要，查看原文内容请购买。
哮喘小鼠模型中气道重构的变化及地塞米松的干预作用
【 ｂｔ ｃ】 Ｏ ｊ ｔ ｅ ｏ ｘｌ ｅ ｈ ｆｃ ｏ ｄｘｍ ｔ ｓ ｅ Ｄ Ｍ） ｎ ｉ ａ ｒ ｏｅ ｎ ｓ ｍ ｔ ｏｓ． ｔ ｄ Ｔ ｅ Ａ ｓａ ｒｔ ｂｃｖ ｅ ｉ Ｔ ｐ ｒ ｔ ｅｅｔ ｆ ｅ ｅ ａ ｎ （ Ｘ ｏ ｒ ｙ ｅ ｄ ｌ ｇ ｎａ ｈ ａ ｃ ｕｅＭｅ ｏ ｓ ｈ ｅ ｏ ｅ ｆ ａ ｈ ｏ ａｗ ｍ ｉ ｉ ｔ ｉｍ ｈ
ｍ ｔ ｏ ｐ ａ ｄ ｔｅＤ Ｍ ｅ ｔ ｒ ｐ ｗ ｒ ｅ ｓ ｉ ｄ ａ ｄ ｒｐ ａｅ ｌ ｃ ａ ｅ ｇ ｄ ｗ ｔ ｏ ａ ｕ ｉ （ Ｖ ｆｒ ｎ ｅ ｋ ． ｈ Ｘ ａ ｃ ｇ ｕ ，ｎ Ｘ ｔ ａ ｄ ｇ ｕ ｅ ｓｎ ｉｚ ｎ ｅ ｅ ｔ ｙ ｈ ｌ ｎ ｅ ｉ ｖ ｂ ｍ ｎ Ｏ Ａ）ｏ ａ ｄ ４ ｗ ｅ ｓ Ｔ ｅＤ Ｍ ｉｒ ｈ ｒ ｅ ｏ ｅ ｔｅ ｄ ｌ ｈ ｌ ２ ｔ ａｅ ｒｕ ｅｅｉｔ ｐ ｒ ｏ ｅ ｊ ｃ ｄ Ｄ Ｍ． ｆ ｒ ｈ ｏ ｌ ｃ ｅ ｅ ，ｈ ｉｅｗ ｒ ｌ ａｅ ． ｈ ｏｉｏ ｈｌ ｒｕ ｄ ｔｅａ ｗ ｙｗ ｓ ｒ ｔ ｇｏ ｐ ｗ ｒ ｒ ｅｉ ｎ ａ ｉ ｅ ｔ Ｘ Ａ ｔ ｅｍ ｄｅ ｓ ｃｄ ｄ ｔｅ ｍ ｃ ｅｅ ａ ｇ ｄ Ｔ ｅｅ ｓ ｐ ｉ ａｏ ｎ ｈ ｉ ａ ａ ｅ ｄ ｎａ ｔ ｌ ｎ ｅ ｅｔ ｕ ｖ ｎ ｒ
气道重构在哮喘发病早期即已出现 ， 并随着病程的延长而加重，
ｆ 关键词】 哮喘； 鼠； 小 气道重构 ； 地塞米松 ； 结缔组织生 长因子
Ｔｈｅ ｅ ｅ ｔｏ ｘａ ｅ ｈａ ｏｎ ｉｗａ ｅ ｏ ｌｎｇ ｉ ｓｈｍ ａ ｉ ｏ ｅ ＷＡＮ Ｇ Ｍ ｉ Ｌ ｉ ＺＨＡＮＧ ａ ｇ— ｕ ． ｆ ｃ ｆｄｅ ｍ ｔ ｓ ｅ ｏｎ ａｒ ｙ ｒ ｍ ｄｅｉ ｎ ａ ｔ ｔｃ ｍ ｕｓ ｎ， ＩＢｅ ， Ｇｕ ｎ ｈ ａｎ
地塞米松对中性粒细胞性哮喘模型小鼠气道炎症的影响
地塞米松对中性粒细胞性哮喘模型小鼠气道炎症的影响摘要】目的：观察地塞米松对中性粒细胞性哮喘（neutrophilic asthma，NA）模型小鼠气道炎症的影响。
方法：C57BL雌性小鼠随机分成NA组、NA地塞米松干预（neutrophilic asthma treating with dexamethasone，NAD）组和正常（NC）组，每组8只。
NA、NAD组予卵蛋白、脂多糖致敏并卵蛋白激发；NAD组激发前腹腔注射地塞米松；NC组不做处理。
小鼠肺功能仪检测气道阻力，以阻力倍增值评价气道反应性；检测支气管肺泡灌洗液（bronchoalveolar lavage fluid，BALF）有核细胞浓度及分类比例；流式细胞术检测脾脏Th17细胞及ki-67+Th17细胞比例；ELISA检测BALF IL-17浓度。
结果（1）NA组气道阻力倍增值显著高于NC组（P<0.05）。
（2）NAD组BALF有核细胞浓度、NEU%、EOS%均显著低于NA组，但仍高于NC组（均P<0.05）。
（3）NAD组脾脏Th17细胞比例显著低于NA组，但仍高于NC组（均P<0.05）；NA、NAD组脾脏ki-67+Th17细胞比例均显著高于NC组（均P<0.05），但NA、NAD组间差异无统计学意义。
（4）NAD组BALF IL-17浓度显著低于NA组，但仍高于NC组（均P<0.05）。
结论：地塞米松可能通过抑制Th17细胞及IL-17表达，减轻NA模型小鼠气道炎症；Th17细胞增殖功能增强且不受地塞米松影响可能与气道炎症持续存在有关。
【关键词】哮喘；中性粒细胞；气道炎症；地塞米松【中图分类号】R965 【文献标识码】A 【文章编号】2095-1752（2015）08-0345-03Effect of dexamethasone on airway inflamation inthe mouse model of neutrophilic asthma【Abstract】Objective To observe the effect of dexamethasone on airway inflammation in the mouse model of Neutrophilic Asthma.Methods Female C57BLmice were randomly divided into NA, NAD and NC group.NA、NAD mice were sensitized by ovalbumin OVA and LPS and challenged by OVA. NAD mice were treated with dexamethasone at beginning of each challenge.NC mice withouttreatment.Airway resistance were measured and fold increase were caculated as an assessment for AHR.Total white blood cell concentration and classification of proportion were determined in the BALF.Percentages of Th17 cells and Ki-67+Th17cells in the spleen were determined by FCM.BALF IL-17 concentration were determined by ELISA. Results (1) Fold increase of airway resistance in the NA group were higher than that of the NC group (each P<0.05).（2）BALF total cell count, neutrophil and eosinophil percentages in the NAD group were lower than that of theNA group (each P<0.05), but were higher than that of the NC group(each P<0.05). (3)Th17 cell percentages in the spleen of the NAD group were lower than that of the NA group, but were higher than that of the NC group(each P<0.05). Ki-67+Th17 cells percentage in the spleen of the NA and NAD group were higher than that of the NC group(each P<0.05);Hoever,no difference were found in the NA group compared with that of the NAD group（4）BALF IL-17 concentration in the NAD group were lower than that of the NA group, but were higher than that of the NC group(each P<0.05). Conclusions Airway inflammation in the mouse model of NA were improved by dexamethasone via its inhibition on the exspression of Th17 cells.The enhanced function of Th17 cells proliferation not influenced by dexamethasone，may be responsible for the persistence of the inflammation.【Keywords】Asthma; Neutrophil;Airway inflammation; Dexamethasone哮喘是最常见的慢性呼吸道疾病，其本质是多种细胞及细胞组分共同参与的慢性气道炎症。
银杏内酯B协同地塞米松对小鼠哮喘模型气道炎症和辅助T细胞亚群影响作用的研究
银杏内酯Ｂ协同地塞米松对小鼠哮喘模型气道炎症和辅助Ｔ细胞亚群影响作用的研究作者：吕进泉张晓鸣吕剑平忻悦唐燕来源：《中国现代医生》2009年第23期[摘要] 目的探讨银杏内酯B协同地塞米松对支气管哮喘气道变应性炎症及辅助T细胞亚群的作用。
方法40只BALB/c小鼠随机分成正常对照组、哮喘对照组、地塞米松组、银杏内酯B组和联合干预组,每组8只。
收集支气管肺泡灌洗液(BALF),行白细胞(WBC)及嗜酸性粒细胞( EOS)计数;应用ELISA法测定BALF中IFN-γ和IL-4水平。
结果BALF中WBC及EOS计数:3个用药组较哮喘对照组明显减少(P[关键词] 支气管哮喘; 银杏内酯B; 气道炎症; T辅助细胞亚群[中图分类号] R969 [文献标识码] A [文章编号] 1673-9701(2009)23-25-02Effects of Ginkgolide B Coordinated with Dexamethasone on Allergic Airway Inflammation and T Helper Cell Subsets in Asthmatic RatsLV Jinquan ZHANG Xiaoming LV Jianping XIN Yue TANG YanPediatrics Department,the Affiliated Hospital of Jiangsu University,Zhenjiang 212001,China[Abstract]ObjectiveTo investigate the effects of Ginkgolide B(GB)coordinatedwith Dexamethasone(DXM)on allergic airway inflammation and T helper cell subsets in asthmatic rats. Methods Forty BALB/c rats were randomly divided into 5 groups equally:the normal group,the asthma model group,the DXM group,the GB group and the DXM+GB group. The WBC count and eosinophil(EOS)count in bronchoalveolar lavage fluid(BALF) were estimated and ELISA was used to determine the concentrations of IFN-γ and IL-4 in BALF. ResultsCompared with the asthma model group,EOS and WBC count and IL-4 level in BALF were significantly lower in the three treated groups(P[Key Words]Asthma; Gingkgolide B; Inflammation; T-lymphocyte cell subsets目前,PAF拮抗剂成为哮喘治疗的研究方向之一,本文探讨天然PAF拮抗剂——银杏内酯B 对哮喘小鼠气道炎症和T辅助细胞(Th)亚群平衡的影响。
地塞米松对哮喘小鼠模型血清CC16的影响
地塞米松对哮喘小鼠模型血清CC16的影响孙惠泉;郝创利;范丽萍;葛春龙【期刊名称】《中国血液流变学杂志》【年(卷),期】2008(018)003【摘要】目的观察腹腔内注射地塞米松对小鼠支气管哮喘模型血清Clara细胞蛋白16(CC16)的影响.方法以30只健康小鼠为实验动物,随机分为3组:即正常组、哮喘组和地塞米松(DEX)组.用卵蛋白致敏、雾化建立豚鼠哮喘模型,用酶联免疫吸附试验检测血清CC16的含量并观察其在组问的含量变化.结果哮喘组小鼠血清中CC16含量明显低于正常对照组(P＜0.05);经DEX预处理后,血清CC16水平较哮喘组明显升高(P＜0.05).结论 CC16参与了哮喘的发病,可能是其中一种重要的内源性抗炎保护因子;而糖皮质激素在哮喘中的抗炎作用可能是通过提高血清CC16的浓度而实现的.【总页数】3页(P335-336,346)【作者】孙惠泉;郝创利;范丽萍;葛春龙【作者单位】苏州大学附属儿童医院,江苏苏州,215003;苏州大学附属儿童医院,江苏苏州,215003;苏州大学附属儿童医院,江苏苏州,215003;苏州大学附属儿童医院,江苏苏州,215003【正文语种】中文【中图分类】R562.25【相关文献】1.射干麻黄汤对哮喘小鼠模型气道炎症及血清IL-6、IL-1O水平的影响 [J], 隋博文;李明虎;翟平平;李明爽;王浩;王达;李成2.哮喘患者血清CC16蛋白检测的临床价值研究 [J], 张悦;王惠萱;陈忠明;杨光辉3.哮喘小鼠模型中气道重构的变化及地塞米松的干预作用 [J], 王敏;李蓓;张光环4.血清CC16含量检测在哮喘诊治中的价值分析 [J], 张悦;陈忠明;王惠萱;杨光辉5.不同控制水平哮喘患儿血清25(OH)D3、CC16水平和FeNO的变化及临床意义[J], 李远哲;郭燕军;胡文洁;施阳;侯杰;林新春;宋晓琴;丁显飞因版权原因，仅展示原文概要，查看原文内容请购买。
地塞米松对哮喘小鼠气道平滑肌细胞中胸腺活化调节趋化因子表达的影响
地塞米松对哮喘小鼠气道平滑肌细胞中胸腺活化调节趋化因子表达的影响张娟;赵铭山【期刊名称】《山东医药》【年(卷),期】2012(52)5【摘要】Objective To observe the influence of expression of dexamethasone on thymus activation regulated chemo-kine(TARC) in asthma smooth muscle cells in asthmatic mice models. Methods Thirty-six mice were randomly divided into three groups: normal control group ( group A), asthma model group ( group B) , and dexamethasone treated group (group C). The asthmatic mice models were established by OVA and AL(OH)3. White cells in BALF and eosinophils (EOS) were counted, HE-stained was used to observe the changes of pulmonary histopathology. The levels of TARC and IL-4 in both serum and BALF were measured by enzyme-linked immunosorbent assay (ELISA), then the expression of TARC protein in airway smooth muscle cells was assessed with immunohistochemistry. Results The total cell numbers and EOS count of group B were significantly higher than those in group A and groupC(P<0.01), EOS counts of group C were higher than those of groupA(P<0.05). The concentrations of TARC and IL-4 in serum of group B were obviously higher than that in group A and group C(P<0.01). The concentrations of TARC and IL-4 in BALF of group B were significantlyhigher than those in group A and group C (P < 0.01); the concentrations of TARC in BALF of group C were higher than those in group A(P <0.01). The protein expressions of TARC in airway smooth muscle cells of group B were significantly higher than those in group A and group C(P <0.01). In mice serum, strong positive correlations were found between TARC and IL-4(r=0.669, P < 0.01) ; there were significant positive correlations between TARC and IL4 in BALF (r=0.845,P<0.01). Conclusions The expressions of TARC in asthma smooth musde cells of asthma mice were significantly higher than those in normal control group. Dexamethasone may inhibit TARC expression through reducing secretion of IL-4.%目的探讨胸腺活化调节趋化因子(TARC)在哮喘小鼠气道平滑肌细胞中的表达及地塞米松对TARC的影响.方法 36只小鼠随机分为对照组(A组)、哮喘模型组(B组)、地塞米松治疗组(C 组),每组12只.以卵白蛋白OVA和氢氧化铝混悬液致敏及OVA激发建立哮喘小鼠模型.行支气管肺泡灌洗液(BALF)沉渣白细胞及嗜酸性粒细胞(EOS)计数,HE染色观察肺组织病理改变,应用酶联免疫吸附实验测定血清及BALF中TARC、IL-4的浓度,并用免疫组织化学的方法测定气道平滑肌细胞中TARC蛋白的表达量.结果 B组白细胞及EOS计数明显高于A、C组(P＜0.01),C组EOS计数高于A组(P＜0.05).B组血清及BALF中TARC及IL-4的浓度显著高于A、C组(P＜0.01)；C组血清、BALF中TARC的浓度低于B组(P＜0.01).B组气道平滑肌细胞中TARC蛋白表达量较A、C组显著增高(P＜0.01).小鼠血清、BALF中TARC浓度与IL-4浓度呈正相关(r=0.669、0.845,P均＜0.01).结论 TARC在哮喘组小鼠肺组织气道平滑肌细胞中的蛋白表达量较正常组明显增多,地塞米松可能通过减少IL-4的分泌从而抑制TARC的表达.【总页数】4页(P25-28)【作者】张娟;赵铭山【作者单位】滨州医学院附属医院,山东滨州256603;滨州医学院附属医院,山东滨州256603【正文语种】中文【中图分类】R562.2【相关文献】1.卡介菌多糖核酸对哮喘小鼠胸腺活化调节趋化因子及mRNA表达的影响 [J], 郑吉善;张正霞;李昌崇;陈庆武;苏苗赏;张维溪;张海邻;董琳;陈小芳;罗运春2.MRL/Ipr小鼠肾组织胸腺和活化调节趋化因子表达检测 [J], 刘海娜;吴春玲;肖卫国3.地塞米松对哮喘小鼠气道平滑肌细胞增殖及转化生长因子β1表达的影响 [J], 刘平莉;吕丽丽;夏春伟;李若然;姚红卫;朱述阳4.地塞米松对哮喘大鼠气道平滑肌细胞增殖及ERK1/2mRNA表达水平的影响 [J], 徐妍;张焕萍5.地塞米松对变应性哮喘小鼠胸腺活化调节趋化因子及mRNA表达的影响 [J], 郑吉善;苏苗赏;李昌崇;叶乐平;董琳;罗运春;陈小芳;李孟荣;张正霞因版权原因，仅展示原文概要，查看原文内容请购买。