兰州大学机构库 >学院待认领
NOTCH信号通路在慢性阻塞性肺疾病免疫失衡中的作用及机制研究
Alternative TitleEffects and mechanisms of NOTCH signaling pathway on immune imbalance in chronic obstructive pulmonary disease
杨鑫娜
Thesis Advisor刘晓菊
2015-05-26
Degree Grantor兰州大学
Place of Conferral兰州
Degree Name硕士
Keyword肺疾病,慢性阻塞性 Notch信号通路 免疫失衡 Notch1 Hes1 Th1 Th2 Th17 Treg
Abstract目的 观察Notch信号通路中Notch1、Jagged1及Hes1对慢阻肺小鼠脾源性CD4+ T淋巴细胞Th1、Th2、Th17、Treg的影响,探讨Notch信号通路在慢阻肺免疫失衡中的作用。方法 Balb/c小鼠120只,随机分为健康组、慢阻肺组、慢阻肺DMSO组和慢阻肺GSI组;建立小鼠慢阻肺模型,观察肺功能及病理变化;检测四种细胞比例及小鼠Notch1、Jagged1和 Hes1 mRNA和蛋白的表达。结果 1. 烟雾暴露90天成功建立小鼠慢阻肺模型,其PIF和PEF值低于健康组,肺内有支气管炎症和肺气肿改变,而健康小鼠无此改变; 2. 慢阻肺组Th1、Th17、Treg细胞比例和Th1/Th2比值较健康组增加,Th2和Th17/Treg未见明显改变;慢阻肺GSI组Th1、Th17、Th1/Th2和Th17/Treg较慢阻肺组减少,Th2和Treg未见明显改变;慢阻肺DMSO组较慢阻肺组均无明显改变。3. 慢阻肺组小鼠Notch1、Jagged1、Hes1 mRNA和蛋白表达较健康组均升高,慢阻肺GSI组较慢阻肺组减少,慢阻肺DMSO组较慢阻肺组无明显改变。4. 相关性分析: 慢阻肺组和慢阻肺GSI组Notch1和Hes1分子的表达与Th1和Th17呈正相关,与Th2和Treg呈负相关;Jagged1分子的表达与此相反。结论1.香烟烟雾暴露可建立小鼠慢阻肺模型;2. 慢阻肺小鼠存在Th1/Th2、Th17/Treg免疫紊乱;3. 慢阻肺小鼠Notch1、Jagged1及Hes1分子mRNA及蛋白水平升高,并与Th1/Th2和Th17/Treg相关;4. GSI能部分抑制Notch1、Jagged1和Hes1及T细胞各亚群水平,表明Notch信号通路参与慢阻肺免疫紊乱。
Other AbstractObjective We observed the influence of the Notch signaling pathway Notch1,Jagged1 and Hes1 in COPD mouse model splenic-derived CD4+ T lymphocyte Th1, Th2, Th17, Treg subsets to explore the roles of Notch signaling pathway on immune imbalance in COPD.Methods 120 of Balb/c mice were randomly assigned into the healthy group, COPD group, COPD Dimethyl sulfoxide (DMSO) group and COPD Gamma secretase inhibitors (GSI) group. Using Cigarette smoke exposure 90 days to establish mouse model of chronic obstructive pulmonary disease, pulmonary function and pathological changes were observed. Flow cytometry was used to detect the proportion of the mouse spleen-derived Th1 cells, Th2 cells,Th17 cells, Treg cells; Using real-time quantitative polymerase chain reaction (RT-PCR) and Western blot (WB) to detect the Alveolar macrophages ligand Jagged1,splenic T lymphocyte’s Notch1 and its downstream Hes1 mRNA and protein expression.Results 1. Smoke exposure 90 days alone, successfully established mouse model of chronic obstructive pulmonary disease. COPD group peak inspiratory flow (PIF) and peak expiratory flow (PEF) was significantly lower than the healthy group, COPD mice lung tissue can be seen bronchitis and emphysema clearly, while no such changes in healthy control mice.2. COPD mice Th1, Th17 and Treg cell percentage compared with the healthy control group, the proportion of cells in mice significantly increased; No significant increase in the proportion of Th2 cells in COPD mice compared with healthy mice; and the proportion of Th1 and Th17 cells in COPD GSI group mice was significantly reduced compared with COPD group, No significant increase in the ratio of Th2 and Treg cells in COPD GSI mice compared with COPD group. COPD group Th1/Th2 ratio compared with the healthy control group was significantly increased; the ratio of Th1/Th2 in COPD GSI Group was significantly lower than COPD group; No significant difference in the ratio of Th1/Th2 in the COPD group and COPD DMSO group. COPD group Th17/Treg ratio compared with the healthy group was increased; and the ratio of Th17/Treg in COPD GSI Group lower than COPD group; Th17/Treg ratio in COPD group and COPD DMSO group had no significant difference. 3. COPD mice Notch1, Jagged1 and Hes1 mRNA and protein expression compared with the healthy group were significantly increased; COPD GSI group Notch1, Jagged1 and Hes1 mRNA and protein expression compared with the COPD group decreased significantly; No significant di...
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Language中文
Document Type学位论文
Identifierhttps://ir.lzu.edu.cn/handle/262010/224012
Collection学院待认领
Affiliation临床医学院
Recommended Citation
GB/T 7714
杨鑫娜. NOTCH信号通路在慢性阻塞性肺疾病免疫失衡中的作用及机制研究[D]. 兰州. 兰州大学,2015.
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