| | | | | 地塞米松对年幼期哮喘大鼠Toll样受体4信号转导的调节机制 | | | 苏苗赏;李昌崇;林立;郑吉善;郑仰明;管小俊;张维溪;罗运春 | | | 目的研究地塞米松(DXM)对哮喘大鼠肺组织Toll样受体4(TLR4)表达的影响,探讨TLR4对嗜酸性粒细胞(EOS)凋亡的调控机制。方法清洁级SD大鼠27只,随机分为对照组、哮喘组、DXM组,每组9只。用卵白蛋白(OVA)致敏与激发建立大鼠哮喘模型。光镜观察肺组织病理变化;BALF中EOS及其他炎症细胞计数;ELISA测定血清OVA-sIgE含量;原位杂交测定肺组织TLR4mRNA表达;TUNEL法检测EOS凋亡。结果(1)肺组织病理变化:哮喘组支气管及血管周围、肺间质及肺泡腔内炎性细胞浸润,支气管黏膜下水肿,黏液腺增生,黏膜皱褶增多,部分黏膜上皮细胞脱落,可见气道黏液栓;DXM组上述现象明显减轻。(2)BALF中炎症细胞计数:哮喘组BALF中细胞总数(4·29±0·12)×109/L、EOS绝对计数(33·94±5·04)×107/L和EOS占细胞总数的百分比(8·50±0·56)%均高于对照组,分别为(2·01±0·10)×109/L、(1·25±0·27)×107/L、(0·56±0·18)%(均P<0·01);DXM组分别为(2·14±0·10)×109/L、(4·78±1·23)×107/L、(2·17±0·25)%,均低于哮喘组(均P<0·01)。(3)血清OVA-sIgE含量检测:哮喘组(83·40±6·80)μg/ml,高于对照组(14·38±4·25)μg/ml(P<0·01);DXM组(45·02±7·47)μg/ml明显低于哮喘组(均P<0·01)。(4)肺组织TLR4mRNA的检测结果(吸光度):TLR(A值)哮喘组(25·81±3·56),对照组(24·71±0·85)(P>0·05);DXM组(33·94±3·28)表达明显高于哮喘组(P<0·01)。(5)EOS凋亡率检测结果,哮喘组(7·39±1·93)%与对照组(9·06±1·52)%比较,两组差异有统计学意义(P<0·05);DXM组(13·33±1·09)%与哮喘组比较明显增高(均P<0·01)。相关分析结果显示,TLR4mRNA表达与EOS凋亡率有中度正相关(r=0·612,P<0·01)。结论DXM降低血清中OVA-sIgE水平,诱导哮喘大鼠肺组织EOS凋亡,可能与激活TLR4信号通路有关。
【作者单位】：温州医学院附属育英儿童医院呼吸内科;温州医学院附属育英儿童医院呼吸内科;温州医学院附属育英儿童医院呼吸内科;宁波市妇女儿童医院儿科;温州医学院附属育英儿童医院呼吸内科;温州医学院附属育英儿童医院呼吸内科;温州医学院附属育英儿童医院呼吸内科;温州医学院附属育英儿童医院呼吸内科
【关键词】：受体,细胞表面;膜糖蛋白;地塞米松;细胞凋亡;哮喘;信号传导
【基金】：浙江省自然科学基金项目(Y205426)
【分类号】：R725.6
【DOI】：CNKI:ISSN:0578-1310.0.2006-12-022
【正文快照】：
儿童哮喘患病率逐年上升[1,2],其发病机制十分复杂,嗜酸性粒细胞性气道炎症是目前公认的变应性哮喘的基本特征之一。Th2细胞的优势应答是导致嗜酸性粒细胞性哮喘(eosinophilic asthma)发生发展的主要免疫学基础。Toll样受体4(TLR4)是一种主要的天然免疫模式识别受体。现代免疫学研究发现,是天然免疫系统的模式识别作用(PRR)触发了T淋巴细胞免疫应答[3]。大量流行病学资料及随之提出的卫生学说认为,生活环境中微生物接触减少可能是引起哮喘发病率持续增高主要原因之一[4,5]。目前在临床中糖皮质激素(GCS)仍是治疗哮喘最有效的方法。然而… | | |  推荐 CAJ下载  PDF下载 | | | CAJViewer7.0阅读器支持所有CNKI文件格式，AdobeReader仅支持PDF格式 | | | | Regulative mechanism of dexamethasone on Toll-like receptor 4 signal transduction of infant asthma rat | | | SU Miao-shang;LI Chang-chong;LIN Li;ZHENG Ji-shan;ZHENG Yang-ming;GUAN Xiao-jun;ZHANG Wei-xi;LUO Yun-chun. Department of Respiratory Diseases;Yuying Children′s Hospital of Wenzhou Medical College;Wenzhou 325027;China | | | Objective Eosinophilic airway inflammation is one of the basic characteristics of allergic asthma.Toll-like receptor is one of the most important innate immunity pattern recognition receptors.Glucocorticoids (GCS) are still the most effective treatment for asthma.However, few reports of studies on regulatory mechanism of GCS on the innate immunity system are available.The mechanism of effects of GCS on TLR4 is unclear.The present study aimed at understanding the effect of dexamethasone (DXM) on change of TLR4 and mechanism of regulatory effect of TLR4 on eosinophil (EOS) apoptosis.Methods Twenty-seven Sprague-Dawley (SD) rats (age 28 to 42 days, body weight 120 to 180 gram) were randomly divided into the control group, asthma group and DXM group with 9 in each.Asthma model rats were sensitized with the mixture of ovalbumin (OVA, 1 mg) and Al(OH)_3, 100 mg on day 1 and day 8, repeatedly exposed to aerosolized OVA after day 15, once a day for three days and continued for 30 minutes at every time.During the sensitization stage, 100 μg/ml DXM were prepared with DXM group for every other day,and the same doses DXM were prepared for every day on the stage of challenge.The histopathological changes of lung tissues were observed with light microscope (LM). EOS and other inflammatory cells in bronchoalveolar lavage fluid (BALF) were counted; the concentrations of OVA-sIgE in serum were measured by using “sandwich” ELISA; The expressions of TLR4 mRNA were determined by in situ hybridization, the apoptosis of EOS was detected by TUNEL.Results (1)LM showed many inflammatory cells infiltration around the bronchi and blood vessels, bronchus mucus increased, airway epithelium damage and desquamation, and airway mucous plugs in asthma group, whereas DXM group showed significantly milder changes. (2)Inflammationary cells count in BALF of asthma group was significantly higher as compared to control group (P<0.01); compared with asthma group, the total cell count, EOS absolute count and EOS% were all significantly decreased in DXM group[(2.14±0.10)×10~9/L, (4.78±1.23)×10~7/L, (2.17±0.25)%]. (3) Levels of OVA-sIgE in serum of asthma group[(83.40±6.80) μg/ml]were significantly higher than those of the control group [(14.38±4.25) μg/ml](P<0.01), while those of DXM group[(45.02±7.47) μg/ml]were significantly lower than asthma group (P<0.0 1). (4) There were no significant differences in TLR4 mRNA detected by in situ hybridization between control group (24.71±0.85) and asthma group (25.81±3.56) (P>0. 05); but it significantly increased in DXM group (29.86±3.92) as compared to asthma group. (5)The percentages of apoptotic EOS in asthma group [(7.39±1.93)%] were significantly lower than those in control group[(9.06±1.52)%](P<0.01); and significantly higher in DXM group[(13.33±1.09)%]than in asthma group (P<0.01). There were significantly positive correlations between TLR4 mRNA and the percentage of apoptotic EOS (r=0.612,P<0.01).Conclusion DXM can decrease OVA-sIgE level, induce EOS apoptosis, which may correlate with the activation of TLR4 signal transduction.
【Keyword】：Receptors,cell surface;Membrane glycoproteins;Dexamethasone;Apoptosis;Asthma;Signal transduction |
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