【摘要】：慢性鼻-鼻竇炎伴息肉(chronic rhinosinusitis with nasal polyps, CRSwNP)是耳鼻咽喉科臨床上常見(jiàn)的、多發(fā)的鼻腔和鼻竇粘膜的慢性炎癥性疾病。根據(jù)目前的流行病學(xué)調(diào)查顯示，CRSwNP在全球范圍內(nèi)的發(fā)病率已高達(dá)2~5%，，其發(fā)生嚴(yán)重影響患者的生活和睡眠質(zhì)量及工作效率，已成為人類主要的公共衛(wèi)生問(wèn)題之一，同時(shí)也帶來(lái)了嚴(yán)重的經(jīng)濟(jì)負(fù)擔(dān)。雖然CRSwNP目前的診療水平已經(jīng)大幅度提高，但是其治療效果依然不能令所有患者滿意，且治療后復(fù)發(fā)率較高。在既往數(shù)十年，臨床耳鼻喉科醫(yī)生及科研工作者對(duì)CRSwNP的病因、發(fā)病機(jī)制和治療進(jìn)行了深入而廣泛的探索和研究。目前認(rèn)為，CRSwNP患者鼻腔和鼻竇粘膜的慢性炎癥主要是由諸如解剖結(jié)構(gòu)異常、感染、變應(yīng)性體質(zhì)、免疫調(diào)節(jié)功能異常等單個(gè)或多個(gè)因素共同作用所致，其中Th17反應(yīng)亢進(jìn)導(dǎo)致的以Th17細(xì)胞過(guò)度活化及其相應(yīng)的相關(guān)促炎細(xì)胞因子的大量釋放是造成國(guó)人CRSwNP發(fā)生發(fā)展的重要原因。 芳香烴受體(aryl hydrocarbon receptor, AhR)，一種依靠配體激活的轉(zhuǎn)錄因子，在調(diào)節(jié)人體免疫反應(yīng)中發(fā)揮了重要作用。已有研究表明它參與了哮喘、特應(yīng)性皮炎、實(shí)驗(yàn)性自身免疫性腦脊髓炎和類風(fēng)濕性關(guān)節(jié)炎等過(guò)敏性和自身免疫性疾病的發(fā)病機(jī)制。近期的動(dòng)物實(shí)驗(yàn)也顯示AhR可通過(guò)控制T淋巴細(xì)胞和樹突細(xì)胞（dendritic cells, DCs)的分化從而發(fā)揮強(qiáng)大的免疫調(diào)節(jié)能力。尤其值得注意的是，AhR一旦被它的天然配體諸如2-（1-吲哚-3-羰基）-噻唑-4-羧酸甲酯(2-(1H-indole-3-carbonyl)-thiazole-4-carboxylic acid methyl ester, ITE)激活，它就能抑制Th17反應(yīng)，進(jìn)而控制慢性炎癥。因此，我們假設(shè)AhR可能參與了CRSwNP患者慢性炎癥的形成。 本實(shí)驗(yàn)的目的是探索AhR在伴變應(yīng)性體質(zhì)和不伴變應(yīng)性體質(zhì)的CRSwNP患者發(fā)病中的作用及其與CRSwNP患者Th17反應(yīng)的相關(guān)性，并予以ITE體外干預(yù)CRSwNP患者和健康對(duì)照來(lái)源的免疫細(xì)胞，探討AhR-DC-Th17信號(hào)通路存在的意義，從而尋找到可能治療該疾病的新的靶點(diǎn)。第一部分CRSwNP患者鼻息肉組織和外周血AhR與Th17反應(yīng) 相關(guān)性研究 目的：通過(guò)檢測(cè)AhR在鼻息肉組織和外周血的表達(dá)，分析其與患者全身及局部Th17反應(yīng)的相關(guān)性，評(píng)估在CRSwNP患者中AhR對(duì)Th17反應(yīng)的調(diào)節(jié)能力，為深入闡明CRSwNP的發(fā)病機(jī)制及為治療該疾病找到新的靶點(diǎn)提供相應(yīng)的理論依據(jù)。 方法：收集48例CRSwNP患者（伴變應(yīng)性體質(zhì)組/atopic組24例；不伴變應(yīng)性體質(zhì)組/non-atopic組24例）的鼻息肉和外周血標(biāo)本和13例腦脊液鼻漏患者（對(duì)照組）的下鼻甲粘膜和外周血標(biāo)本。檢測(cè)AhR (RT-qPCR及Western blot檢測(cè)法)、RORC (RT-qPCR檢測(cè)法)、IL-17和IL-10(ELISA檢測(cè)法)的表達(dá)水平及Th17細(xì)胞的比率(流式細(xì)胞術(shù))。 結(jié)果：CRSwNP患者鼻息肉組織和外周血中AhR的表達(dá)水平較對(duì)照組顯著降低，且atopic組的表達(dá)水平較non-atopic組更低，差異有統(tǒng)計(jì)學(xué)意義；然而，CRSwNP患者鼻息肉組織RORC水平較對(duì)照組顯著升高，外周血Th17細(xì)胞及IL-17水平亦較對(duì)照組明顯升高，且三者在atopic組的水平均較non-atopic組更高，差異具有統(tǒng)計(jì)學(xué)意義。CRSwNP患者鼻息肉組織AhR表達(dá)水平與RORC及IL-17水平均呈負(fù)相關(guān)，外周血AhR表達(dá)水平與Th17比率及IL-17水平亦呈負(fù)相關(guān)；而CRSwNP患者鼻息肉組織AhR水平與外周血AhR水平呈高度正相關(guān)，鼻息肉組織RORC及IL-17水平與外周血Th17比率及IL-17水平亦呈高度正相關(guān)。 結(jié)論：AhR的表達(dá)降低及過(guò)度的Th17反應(yīng)存在于CRSwNP患者的鼻息肉組織及外周血中，由于AhR表達(dá)的降低而引起的鼻息肉組織及外周血的Th17反應(yīng)在CRSwNP患者的發(fā)病機(jī)制中可能扮演著重要的角色；而atopic組表現(xiàn)為更低的AhR表達(dá)及更嚴(yán)重的Th17反應(yīng)，提示變應(yīng)性因素可能通過(guò)降低AhR表達(dá)從而加劇Th17反應(yīng)。 第二部分AhR配體對(duì)CRSwNP患者PBMCs中Th17反應(yīng)的干預(yù)調(diào)控研究 目的：通過(guò)將AhR配體ITE作為干預(yù)手段，觀察ITE干預(yù)的兩組CRSwNP患者PBMCs中AhR表達(dá)、Th17比率、IL-17和IL-10水平的變化情況，分析AhR-Th17及其相關(guān)細(xì)胞因子在CRSwNP發(fā)生發(fā)展中所扮演的角色，并在前一部分實(shí)驗(yàn)基礎(chǔ)上，體外證實(shí)AhR配體ITE可抑制CRSwNP患者的Th17反應(yīng)，從而達(dá)到在一定程度上控制炎癥的目的。 方法：收集18例CRSwNP患者（atopic組9例；non-atopic組9例）和9例腦脊液鼻漏的外周血標(biāo)本，分離得到PBMCs后予以ITE干預(yù)。采用Western blot檢測(cè)兩組CRSwNP患者PBMCs中AhR表達(dá)水平；采用流式細(xì)胞術(shù)檢測(cè)PBMCs中Th17細(xì)胞比率；采用ELISA檢測(cè)PBMCs培養(yǎng)上清液中IL-17及IL-10的水平。 結(jié)果：通過(guò)ITE干預(yù)后，兩組CRSwNP患者PBMCs中AhR表達(dá)均升高，而Th17細(xì)胞比率和IL-17水平則顯著降低。此外，IL-10的水平在ITE干預(yù)后顯著升高。 結(jié)論：AhR的表達(dá)可在ITE的作用下升高，并參與抑制Th17反應(yīng)和促進(jìn)IL-10的產(chǎn)生，揭示了AhR在調(diào)控Th17反應(yīng)中發(fā)揮著負(fù)調(diào)節(jié)子的功能，證實(shí)了ITE可通過(guò)AhR-Th17信號(hào)通路抑制CRSwNP患者的炎癥反應(yīng)。 第三部分樹突細(xì)胞和T細(xì)胞中AhR及相關(guān)細(xì)胞因子的表達(dá)水平的研究 目的：通過(guò)檢測(cè)兩組CRSwNP患者及健康對(duì)照組外周血來(lái)源的DCs和CD4+T細(xì)胞AhR表達(dá)及相關(guān)細(xì)胞因子的分泌水平，以期找到免疫調(diào)節(jié)過(guò)程中AhR作用的靶點(diǎn)。 方法：收集18例CRSwNP患者（atopic組9例；non-atopic組9例）和9例健康成年人的外周血標(biāo)本，通過(guò)各自磁珠分選得到單核細(xì)胞和CD4+T細(xì)胞；一方面將單核細(xì)胞通過(guò)培養(yǎng)7天誘導(dǎo)為DCs；另一方面直接將分選的CD4+T細(xì)胞培養(yǎng)3天。采用RT-qPCR和Western Blot方法檢測(cè)DCs和CD4+T細(xì)胞AhR的表達(dá)；；采用ELISA檢測(cè)細(xì)胞培養(yǎng)上清液中IL-1β、IL-6、IL-10、和IL-17的水平。 結(jié)果：CRSwNP患者DCs中AhR的表達(dá)水平較對(duì)照組顯著降低，且atopic組的表達(dá)水平較non-atopic組更低，差異有統(tǒng)計(jì)學(xué)意義；而三組的CD4+T細(xì)胞AhR表達(dá)無(wú)明顯差異，經(jīng)過(guò)統(tǒng)計(jì)學(xué)分析差異無(wú)意思。CRSwNP患者DCs分泌促炎性細(xì)胞因子IL-1β和IL-6增加，同時(shí)抗炎性細(xì)胞因子IL-10的分泌減少；而CRSwNP患者CD4+T細(xì)胞分泌促炎性細(xì)胞因子IL-17增高，而抗炎性細(xì)胞因子IL-10的分泌降低；且atopic CRSwNP患者組和Non-atopic CRSwNP患者組細(xì)胞因子水平均存在明顯的統(tǒng)計(jì)學(xué)差異。 結(jié)論：我們的研究表明DCs中AhR的缺陷可能是導(dǎo)致Th17反應(yīng)的靶點(diǎn)，AhR在DCs的活化可能在調(diào)控抗炎反應(yīng)中起關(guān)鍵作用。此外，AhR的缺陷在伴有atopy的CRSwNP患者更加嚴(yán)重，這也提示我們變應(yīng)性因素可能也是通過(guò)AhR信號(hào)通路進(jìn)而加重CRSwNP患者的Th17反應(yīng)。 第四部分AhR配體通過(guò)干預(yù)樹突細(xì)胞和T細(xì)胞抑制CRSwNP患者的Th17反應(yīng) 目的：通過(guò)AhR配體ITE干預(yù)兩組CRSwNP患者外周血來(lái)源的DCs和CD4+T細(xì)胞，分析ITE通過(guò)AhR-DCs-CD4+T細(xì)胞軸和AhR-CD4+T細(xì)胞軸對(duì)Th17反應(yīng)的影響。 方法：收集20例CRSwNP患者（atopic組10例；non-atopic組10例）和12例健康成年人的外周血標(biāo)本，通過(guò)各自磁珠分選得到單核細(xì)胞和CD4+T細(xì)胞；一方面將單核細(xì)胞誘導(dǎo)為DCs，并予以ITE干預(yù)后與CD4+T細(xì)胞共培養(yǎng)；另一方面直接予以ITE干預(yù)CD4+T細(xì)胞。采用RT-qPCR方法檢測(cè)DCs和CD4+T細(xì)胞AhR的表達(dá)；采用流式細(xì)胞術(shù)檢測(cè)Th17細(xì)胞比率；采用ELISA檢測(cè)細(xì)胞培養(yǎng)上清液中IL-1β、IL-6、IL-10、和IL-17的水平。 結(jié)果：予以ITE干預(yù)DCs后,能顯著抑制DCs分泌促炎性細(xì)胞因子IL-1β和IL-6的分泌，同時(shí)促進(jìn)抗炎性細(xì)胞因子IL-10的分泌；予以ITE干預(yù)CD4+T細(xì)胞后，能明顯抑制CD4+T細(xì)胞分泌促炎性細(xì)胞因子IL-17和促進(jìn)抗炎性細(xì)胞因子IL-10的分泌；同時(shí)抑制Th17細(xì)胞的分化。 結(jié)論：ITE可通過(guò)作用于DCs和CD4+T細(xì)胞從而抑制Th17反應(yīng)并控制CRSwNP患者的炎癥反應(yīng)；AhR-DCs-Th17細(xì)胞軸可能是治療CRSwNP患者的重要信號(hào)通路。ITE作為一種無(wú)毒的AhR配體，能夠在體外明顯抑制CRSwNP患者的Th17反應(yīng)，因此，它將來(lái)可能成為治療CRSwNP患者的潛在候選藥物。
[Abstract]:Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common chronic inflammatory disease of the nasal cavity and sinus mucosa in otolaryngology. According to the current epidemiological investigation, the incidence of CRSwNP in the world has reached 2-5%, which seriously affects the lives and lives of patients. Sleep quality and work efficiency have become one of the major public health problems of mankind, but also brought serious economic burden. Although the level of diagnosis and treatment of CRSwNP has been greatly improved, its treatment effect is still unsatisfactory to all patients, and the recurrence rate after treatment is high. In the past decades, clinical otolaryngologists At present, it is believed that the chronic inflammation of nasal cavity and sinus mucosa in CRSwNP patients is mainly caused by single or multiple factors such as abnormal anatomy, infection, allergic constitution, and abnormal immune regulation, among which Th17 The overactivation of Th17 cells and the release of inflammatory cytokines are the important reasons for the development of CRSwNP in Chinese.
Aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, plays an important role in regulating human immune response. It has been shown to be involved in the pathogenesis of allergic and autoimmune diseases such as asthma, atopic dermatitis, experimental autoimmune encephalomyelitis and rheumatoid arthritis. Recent animal studies have also shown that AhR exerts powerful immune regulation by controlling the differentiation of T lymphocytes and dendritic cells (DCs). It is particularly noteworthy that once AhR is subjected to its natural ligands such as 2-(1-indole-3-carbonyl) -thiazole-4-carboxylic acid methyl ester (2-(1H-indole-3-carbonyl) -thiazole-4-carb Activation of oxylic acid methyl ester (ITE) can inhibit Th17 response and thus control chronic inflammation. Therefore, we hypothesize that AhR may be involved in the formation of chronic inflammation in CRSwNP patients.
The purpose of this study was to explore the role of AhR in the pathogenesis of CRSwNP patients with allergic constitution and non-allergic constitution and its correlation with Th17 reaction in CRSwNP patients. ITE was given to intervene in vitro the immune cells from CRSwNP patients and healthy controls, and to explore the significance of AhR-DC-Th17 signaling pathway in order to find possible treatment. The new target of the disease. Part I: AhR and Th17 reaction in nasal polyps and peripheral blood of CRSwNP patients
Correlation study
AIM: To investigate the expression of AhR in nasal polyps and peripheral blood, analyze its correlation with systemic and local Th17 response, and evaluate the regulation of AhR on Th17 response in patients with CRSwNP.
Methods: 48 patients with CRSwNP (24 patients with allergic constitution / atopic group; 24 patients without allergic constitution / non-atopic group) and 13 patients with cerebrospinal fluid rhinorrhea (control group) were collected for nasal polyps and peripheral blood samples. The expression level of IL-10 (ELISA assay) and the ratio of Th17 cells (flow cytometry).
Results: The expression level of AhR in nasal polyps and peripheral blood of CRSwNP patients was significantly lower than that of control group, and the expression level of AhR in atopic group was lower than that of non-atopic group. However, the RORC level in nasal polyps of CRSwNP patients was significantly higher than that of control group, and the levels of Th17 cells and IL-17 in peripheral blood were also significantly higher than that of control group. The expression of AhR in nasal polyps of CRSwNP patients was negatively correlated with RORC and IL-17 levels, and the expression of AhR in peripheral blood was negatively correlated with Th17 ratio and IL-17 level, while the level of AhR in nasal polyps of CRSwNP patients was negatively correlated with that in peripheral blood. RORC and IL-17 levels in nasal polyps were positively correlated with Th17 ratio and IL-17 level in peripheral blood.
CONCLUSION: Decreased AhR expression and excessive Th17 reaction are present in nasal polyps and peripheral blood of CRSwNP patients. Th17 reaction in nasal polyps and peripheral blood may play an important role in the pathogenesis of CRSwNP patients caused by decreased AhR expression, whereas lower expression and more severe Th17 reaction may be found in atopic patients. The Th17 reaction suggests that allergic factors may aggravate the Th17 response by decreasing the expression of AhR.
The second part is the intervention and regulation of AhR ligand on Th17 response in PBMCs of CRSwNP patients.
AIM: To observe the changes of AhR expression, Th17 ratio, IL-17 and IL-10 levels in PBMCs of two groups of CRSwNP patients treated with ITE, and to analyze the role of AhR-Th17 and its related cytokines in the development of CRSwNP. The Th17 reaction of SwNP patients can achieve the purpose of controlling inflammation to some extent.
Methods: 18 patients with CRSwNP (9 in atopic group, 9 in non-atopic group) and 9 patients with cerebrospinal fluid rhinorrhea (CSF rhinorrhea) were collected. PBMCs were isolated and treated with ITE. The expression of AhR in PBMCs was detected by Western blot, the Th17 cell ratio in PBMCs was detected by flow cytometry, and the PBMCs culture was detected by ELISA. The level of IL-17 and IL-10 in clear liquid.
Results: After ITE intervention, the expression of AhR in PBMCs of CRSwNP patients in both groups increased, while the ratio of Th17 cells and the level of IL-17 decreased significantly. In addition, the level of IL-10 increased significantly after ITE intervention.
CONCLUSION: The expression of AhR can be elevated under the action of ITE, and is involved in inhibiting Th17 response and promoting IL-10 production. It reveals that AhR plays a negative regulatory role in regulating Th17 response, which confirms that ITE can inhibit inflammation in CRSwNP patients through AhR-Th17 signaling pathway.
The third part is the expression level of AhR and related cytokines in dendritic cells and T cells.
AIM: To detect the expression of AhR and the secretion of cytokines in peripheral blood-derived DCs and CD4 + T cells from CRSwNP patients and healthy controls in order to find the target of AhR in the process of immunoregulation.
Methods: Monocytes and CD4 + T cells were isolated from peripheral blood samples of 18 patients with CRSwNP (9 cases in atopic group, 9 cases in non-atopic group) and 9 healthy adults by magnetic beads sorting. Monocytes were induced into DCs after 7 days of culture, and CD4 + T cells were cultured directly for 3 days. RT-qPCR and Western B PCR were used. The expression of AhR in DCs and CD4+T cells was detected by lot assay
Results: The expression level of AhR in DCs of CRSwNP patients was significantly lower than that of control group, and the expression level of AhR in atopic group was lower than that of non-atopic group, the difference was statistically significant; but the expression of AhR in CD4 + T cells of three groups was not significantly different, and the difference was insignificant after statistical analysis. The secretion of anti-inflammatory cytokine IL-10 decreased, while that of pro-inflammatory cytokine IL-17 and anti-inflammatory cytokine IL-10 increased in CD4+T cells of CRSwNP patients and decreased in non-atopic CRSwNP patients.
CONCLUSION: Our study suggests that the deficiency of AhR in DCs may be the target of Th17 reaction, and the activation of AhR in DCs may play a key role in regulating anti-inflammatory response. In addition, the deficiency of AhR is more serious in CRSWNP patients with atopy, suggesting that allergic factors may also aggravate CRSwNP through AhR signaling pathway. The Th17 reaction.
The fourth part of the AhR ligand inhibits the Th17 response in CRSwNP patients by interfering with dendritic cells and T cells.
AIM: To investigate the effects of AhR ligand ITE on the Th17 response of peripheral blood-derived DCs and CD4 + T cells in two groups of CRSwNP patients.
Methods: Twenty patients with CRSwNP (10 patients in atopic group; 10 patients in non-atopic group) and twelve healthy adults were collected. Monocytes and CD4 + T cells were isolated by magnetic beads. Monocytes were induced into DCs and co-cultured with CD4 + T cells after ITE intervention. The expression of AhR in DCs and CD4+T cells was detected by RT-q PCR, the ratio of Th17 cells was detected by flow cytometry, and the levels of IL-1beta, IL-6, IL-10 and IL-17 in the supernatant were detected by ELISA.
Results: ITE could significantly inhibit the secretion of pro-inflammatory cytokines IL-1beta and IL-6, and promote the secretion of anti-inflammatory cytokines IL-10. ITE could significantly inhibit the secretion of pro-inflammatory cytokine IL-17 and anti-inflammatory cytokine IL-Th10 in CD4+T cells. 7 cell differentiation.
CONCLUSION: ITE can inhibit Th17 reaction and control inflammation in CRSwNP patients by acting on DCs and CD4+T cells, and the AhR-DCs-Th17 cell axis may be an important signaling pathway in the treatment of CRSwNP patients. Potential candidate drugs for CRSwNP patients.
【學(xué)位授予單位】：重慶醫(yī)科大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2014
【分類號(hào)】：R765.21

【共引文獻(xiàn)】

相關(guān)期刊論文 前10條

1 王海樹;袁紅海;潘三強(qiáng);宿寶貴;;TCDD宮內(nèi)暴露對(duì)子鼠肝細(xì)胞和亞細(xì)胞結(jié)構(gòu)的毒性作用[J];解剖學(xué)研究;2013年04期

2 Gui-lin Yang;Ying-xia Liu;Mu-tong Fang;Wei-long Liu;Xin-chun Chen;John Nunnari;Jing-jing Xie;Ming-feng Liao;Ming-xia Zhang;Guo-bao Li;Pei-ze Zhang;Yi Guan;Bo-ping Zhou;;Higher Viral Load and Prolonged Viral Shedding Period is Associated with Impaired Th17 Cell Response in Patients with H1N1 Influenza A[J];Infection International(Electronic Edition);2012年03期

3 胡瑛;李寶蘭;;缺氧誘導(dǎo)因子-1α、2α在惡性腫瘤中不同作用的研究進(jìn)展[J];癌癥進(jìn)展;2014年02期

4 封少龍;曾燦;楊峗;曹朝暉;;芳香烴受體在腫瘤發(fā)生發(fā)展過(guò)程中的作用[J];癌變.畸變.突變;2014年03期

5 伯銘羽;王向東;張羅;;基質(zhì)金屬蛋白酶及其組織抑制因子在慢性鼻-鼻竇炎中的研究進(jìn)展[J];中國(guó)耳鼻咽喉頭頸外科;2014年04期

6 蔡建良;官樹雄;麥周生;章詩(shī)富;;變應(yīng)性及非變應(yīng)性鼻炎患者白細(xì)胞介素-16、17的表達(dá)及意義[J];廣東醫(yī)學(xué);2014年09期

7 羅晨煜;;我國(guó)電子垃圾回收與健康保護(hù)機(jī)制[J];經(jīng)營(yíng)管理者;2014年32期

8 張沈華;申聰香;文忠;李冠雪;楊柯柯;史欣;;Nods樣模式識(shí)別受體在鼻息肉組織中的表達(dá)及意義[J];臨床耳鼻咽喉頭頸外科雜志;2013年20期

9 Jing Bai;Xiaomin Sun;Chenxi Zhang;Chen Gong;Jingtian Hu;Jianghua Zhang;;Mechanism and kinetics study on the ozonolysis reaction of 2,3,7,8-TCDD in the atmosphere[J];Journal of Environmental Sciences;2014年01期

10 楊敏;韓吉龍;岳耀敬;史兆國(guó);郭婷婷;吳瑜瑜;王朝風(fēng);郭健;劉建斌;孫曉萍;牛春娥;楊博輝;;藏羊HIF-1α基因CDS區(qū)多態(tài)性及生物信息學(xué)分析[J];江蘇農(nóng)業(yè)科學(xué);2013年10期

相關(guān)會(huì)議論文 前1條

1 程曉蕾;陳宏;;Th17細(xì)胞與變態(tài)反應(yīng)性疾病的研究現(xiàn)狀[A];第六次全國(guó)中西醫(yī)結(jié)合變態(tài)反應(yīng)學(xué)術(shù)大會(huì)論文匯編[C];2013年

相關(guān)博士學(xué)位論文 前10條

1 吳俊華;鼻息肉組織中BMP信號(hào)活性及E-cadherin表達(dá)失調(diào)與疾病進(jìn)展的相關(guān)性研究[D];華中科技大學(xué);2010年

2 劉火旺;復(fù)發(fā)性鼻息肉分子標(biāo)志物篩選及其意義[D];中南大學(xué);2010年

3 付志婕;經(jīng)典型瞬時(shí)感受器電位通道在鼻息肉中的作用及機(jī)制研究[D];山東大學(xué);2013年

4 李旭;ROS依賴的內(nèi)質(zhì)網(wǎng)應(yīng)激—自噬反應(yīng)在醉茄素A誘導(dǎo)人胰腺癌細(xì)胞凋亡中的作用研究[D];華中科技大學(xué);2013年

5 胡雙;克拉霉素和地塞米松在不同類型CRS中作用的初步探討[D];華中科技大學(xué);2013年

6 袁立來(lái);典型多環(huán)芳烴暴露對(duì)稀有泩?chǎng)a藥物代謝系統(tǒng)相關(guān)基因表達(dá)的影響[D];華中農(nóng)業(yè)大學(xué);2013年

7 敬曉棋;乳腺炎細(xì)胞因子及T淋巴細(xì)胞亞群研究[D];西北農(nóng)林科技大學(xué);2013年

8 寇巍;鼻息肉患者Treg/Th17細(xì)胞表達(dá)與TGF-β1相關(guān)性及鼻用激素干預(yù)的研究[D];重慶醫(yī)科大學(xué);2013年

9 王曉強(qiáng);STAT3信號(hào)通路在鼻息肉發(fā)病機(jī)制中作用的初步研究[D];重慶醫(yī)科大學(xué);2013年

10 羅啟慧;肺炎鏈球菌感染獼猴腸道菌群分子解析及消化、呼吸、免疫系統(tǒng)免疫相關(guān)因子的表達(dá)[D];四川農(nóng)業(yè)大學(xué);2012年

相關(guān)碩士學(xué)位論文 前10條

1 阮麗君;RVVC證候特點(diǎn)與患者陰道局部IL-4、IL-12、IFN-γ水平的研究[D];廣州中醫(yī)藥大學(xué);2012年

2 趙淑敏;山東地區(qū)慢性鼻—鼻竇炎患者診療認(rèn)識(shí)度的問(wèn)卷調(diào)查[D];山東大學(xué);2013年

3 齊瑩;基于離子液體/納米材料復(fù)合的電化學(xué)傳感器在環(huán)境激素分析中的應(yīng)用[D];湘潭大學(xué);2012年

4 錢亞f;中鼻甲泡與鼻中隔偏曲及兩者與慢性鼻—鼻竇炎關(guān)系[D];浙江大學(xué);2012年

5 房光萃;自身免疫性心肌炎中Th17/Treg細(xì)胞的變化與意義[D];福建醫(yī)科大學(xué);2013年

6 石小偉;晉西北某地變應(yīng)性鼻炎的發(fā)病特點(diǎn)及Th17、CD4~+CD25~+Foxp3~+調(diào)節(jié)性T細(xì)胞在外周血中的表達(dá)[D];安徽醫(yī)科大學(xué);2013年

7 余茜;芳香烴受體及相關(guān)基因在人皮脂腺細(xì)胞上表達(dá)及其意義的研究[D];安徽醫(yī)科大學(xué);2013年

8 黃方杰;重癥肌無(wú)力發(fā)病機(jī)制以及相關(guān)自身抗體研究[D];天津醫(yī)科大學(xué);2013年

9 于小璇;Th17、Treg細(xì)胞以及相關(guān)細(xì)胞因子與尋常型天皰瘡發(fā)病相關(guān)性的研究[D];昆明醫(yī)科大學(xué);2013年

10 高辰;指示非二VA英類多氯聯(lián)苯和植物生長(zhǎng)素的新型報(bào)告體系的構(gòu)建[D];浙江大學(xué);2013年

本文編號(hào)：2192928