本文選題：SOCS-3 + 支氣管哮喘　； 參考：《吉林大學(xué)》2013年碩士論文

【摘要】：支氣管哮喘的特征性表現(xiàn)有慢性氣道炎癥、可逆性氣道阻塞、氣道高反應(yīng)性（AHR，非特異性刺激后因氣流阻塞增強(qiáng)而產(chǎn)生）、黏液過(guò)度分泌及上皮的纖維化。該類患者的支氣管周圍可見(jiàn)大量嗜酸性粒細(xì)胞、淋巴細(xì)胞的浸潤(rùn)。Th2細(xì)胞是浸潤(rùn)支氣管哮喘病人氣道的主要淋巴細(xì)胞亞群，其分泌的細(xì)胞因子（IL-4、IL-5、IL-13）與氣道嗜酸性粒細(xì)胞增多、氣道高反應(yīng)性及血清IgE增加等一系列癥狀的發(fā)生密切相關(guān)。這些細(xì)胞因子首先與細(xì)胞表面的受體結(jié)合，然后激活信號(hào)轉(zhuǎn)導(dǎo)復(fù)合物，包括JAK和STAT，以及Ras-細(xì)胞外信號(hào)調(diào)解激酶，繼而產(chǎn)生效應(yīng)。 SOCS是一類抑制JAK-STAT信號(hào)通路的蛋白家族分子，該蛋白能夠調(diào)解Th細(xì)胞的分化。其中Th2細(xì)胞高表達(dá)SOCS-3蛋白，在Th2細(xì)胞中，IL-12介導(dǎo)的STAT活化途徑被抑制。SOCS-3抑制該途徑是通過(guò)結(jié)合IL-12受體的β亞基中的STAT-4的位點(diǎn)來(lái)實(shí)現(xiàn)的。在支氣管哮喘或者非特異性皮炎患者體內(nèi)，，T細(xì)胞的SOCS-3轉(zhuǎn)錄物的表達(dá)水平與血清IgE水平及疾病的嚴(yán)重程度密切相關(guān)。T細(xì)胞中的SOCS-3基因的表達(dá)導(dǎo)致OVA誘導(dǎo)的過(guò)敏性哮喘小鼠模型的Th2型細(xì)胞分化、氣道的嗜酸性粒細(xì)胞增加以及AHR增強(qiáng)。有實(shí)驗(yàn)證明T細(xì)胞中缺乏SOCS-3基因的小鼠的Th1和Th2細(xì)胞分化減少，向Th3細(xì)胞分化增加，從而導(dǎo)致轉(zhuǎn)化生長(zhǎng)因子β（TGF-β）產(chǎn)生增加。且已有研究表明，SOCS-3能夠抑制CD4+CD25+Foxp3+調(diào)節(jié)性T細(xì)胞的增殖及其功能。因此，下調(diào)T細(xì)胞中的SOCS-3的表達(dá)對(duì)支氣管哮喘的的治療可能有作用。 本研究是將課題組前期已設(shè)計(jì)并鑒定其沉默效率的特異性SOCS-3siRNA慢病毒載體，經(jīng)體內(nèi)轉(zhuǎn)染BALB/c哮喘小鼠模型，留取肺組織標(biāo)本及血清，應(yīng)用HE染色、剛果紅染色、ELISA、免疫組織化學(xué)、RT-PCR和Western Blot等實(shí)驗(yàn)方法比較SOCS-3siRNA慢病毒載體體內(nèi)轉(zhuǎn)染對(duì)哮喘小鼠氣道炎癥及Th1/Th2比例平衡的影響。本實(shí)驗(yàn)采用基因沉默的方法，沉默SOCS-3基因，達(dá)到改善哮喘小鼠模型的哮喘癥狀的目的，以期為支氣管哮喘的臨床研究與治療提供理論及實(shí)驗(yàn)依據(jù)。
[Abstract]:The characteristic manifestations of bronchial asthma include chronic airway inflammation reversible airway obstruction airway hyperresponsiveness AHRs increased airflow obstruction after nonspecific stimulation mucus hypersecretion and epithelial fibrosis. A large number of eosinophilic granulocytes were found around the bronchi of these patients. The infiltration of lymphocytes. Th2 cells were the main lymphocyte subsets in the airway of asthmatic patients. The cytokines secreted IL-4 / IL-5 / IL-13) and the number of eosinophils in the airway were increased. A series of symptoms such as airway hyperresponsiveness and increased serum IgE are closely related. These cytokines first bind to receptors on the cell surface and then activate signal transduction complexes, including JAK and stat, as well as Ras-extracellular signal-mediated kinases. SOCS is a family of proteins that inhibit the JAK-STAT signaling pathway and mediate the differentiation of Th cells. The overexpression of SOCS-3 protein in Th2 cells was inhibited by the inhibition of STAT activation pathway mediated by IL-12 in Th2 cells. SOCS-3 inhibited this pathway by binding the STAT-4 site in 尾 subunit of IL-12 receptor. Expression of SOCS-3 transcripts in T cells of patients with bronchial asthma or nonspecific dermatitis is closely related to serum IgE level and severity of disease. The expression of SOCS-3 gene in T cells leads to OVA induced allergic asthma. Differentiation of Th2 type cells in asthmatic mice, Airway eosinophilic granulocytes increased and AHR increased. Some experiments have proved that the differentiation of Th1 and Th2 cells in mice lacking SOCS-3 gene in T cells decreased, and the differentiation to Th3 cells increased, which resulted in the increase of TGF- 尾 production. It has been shown that SOCS-3 can inhibit the proliferation and function of CD4 CD25 Foxp3 regulatory T cells. Therefore, down-regulation of SOCS-3 expression in T cells may play a role in the treatment of bronchial asthma. In this study, we designed and identified the specific SOCS-3siRNA lentivirus vector with silencing efficiency, transfected BALB/c asthma mouse model in vivo, collected lung tissue and serum, and used HE staining. The effects of SOCS-3siRNA lentivirus vector transfection on airway inflammation and Th1/Th2 balance in asthmatic mice were compared by Congo red staining Elisa immunohistochemistry RT-PCR and Western Blot. In this study, gene silencing was used to silence the SOCS-3 gene to improve the asthmatic symptoms in mice model of asthma, in order to provide theoretical and experimental basis for the clinical study and treatment of bronchial asthma.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2013
【分類號(hào)】：R562.25

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 祖瑩;李成榮;李德發(fā);鄧?yán)^巋;鄭躍杰;;細(xì)胞因子信號(hào)抑制因子在支氣管哮喘T_H1／T_H2細(xì)胞失衡中的作用[J];中華微生物學(xué)和免疫學(xué)雜志;2006年06期

本文編號(hào)：1966379