【摘要】：目的：盡管TSLP, IL-25和IL-33在Th2反應(yīng)的啟動(dòng)和發(fā)展中發(fā)揮了作用,但它們?cè)谑人崃＜?xì)胞性及非嗜酸粒細(xì)胞性伴鼻息肉的慢性鼻-鼻竇炎Th反應(yīng)的形成中所起的作用仍然不明。此研究旨在進(jìn)一步探索TSLP,IL-25,IL-33和它們的受體在伴鼻息肉的慢性鼻-鼻竇炎中的表達(dá)關(guān)聯(lián),以及它們?cè)谌吮钦衬ど掀ぜ?xì)胞中的相互調(diào)控機(jī)制。 方法：我們運(yùn)用了免疫組織化學(xué),實(shí)時(shí)定量PCR,酶聯(lián)免疫吸附試驗(yàn),Bio-Plex懸液芯片和流式細(xì)胞檢測(cè)技術(shù)檢測(cè)TSLP/TSLP受體(TSLPR)/IL-7受體α(IL-7Ra), IL-25/IL-17B受體(IL-17RB),和IL-33/膜型ST2(ST2L)/可溶型ST2(sST2)在鼻竇粘膜以及人鼻粘膜上皮細(xì)胞中的表達(dá)；應(yīng)用人原代鼻粘膜上皮細(xì)胞氣液交換面培養(yǎng)探究細(xì)胞因子及其受體在上皮細(xì)胞中的表達(dá)調(diào)控。 結(jié)果：嗜酸粒細(xì)胞性伴鼻息肉的慢性鼻-鼻竇炎相對(duì)于對(duì)照組和非嗜酸性伴鼻息肉的慢性鼻-鼻竇炎,TSLP/TSLPR/lL-7Ra和ST2L/sST2的信使RNA水平和蛋白質(zhì)水平的表達(dá)在上皮細(xì)胞和間質(zhì)均顯著增高,尤其在上皮細(xì)胞中最明顯。但I(xiàn)L-25/IL-17RB和IL-33在嗜酸粒細(xì)胞性伴鼻息肉的慢性鼻-鼻竇炎中并不增高。TSLP, TSLPR和ST2L的表達(dá)水平與嗜酸粒細(xì)胞性伴鼻息肉的慢性鼻-鼻竇炎的VAS評(píng)分、CT評(píng)分和所有組鼻竇粘膜中Th2細(xì)胞因子的表達(dá)呈正相關(guān)。ST2L的表達(dá)與TSLP及其受體的表達(dá)呈顯著正相關(guān)。在人原代鼻粘膜上皮細(xì)胞培養(yǎng)中,TSLP可以誘導(dǎo)ST2L的表達(dá),IL-33可以通過(guò)上調(diào)的ST2L再進(jìn)一步促進(jìn)TSLP的表達(dá)增加。另外,TSLP/TSLPR/IL-7Ra和ST2L可以由Th2型細(xì)胞因子誘導(dǎo)產(chǎn)生,然而,IL-25/IL-17RB和IL-33的表達(dá)可以被Th1/Th17型細(xì)胞因子分別上調(diào)。 結(jié)論：在嗜酸粒細(xì)胞性伴鼻息肉的慢性鼻-鼻竇炎中,TSLP, IL-33及它們的受體形成的正反饋環(huán)和Th2細(xì)胞因子都可以促進(jìn)Th2炎癥反應(yīng)的發(fā)生發(fā)展。 目的：呼吸道病毒被認(rèn)為是急性鼻-鼻竇炎的一個(gè)啟動(dòng)因素,但是其在慢性鼻-鼻竇炎(CRS)中的作用尚不清楚。本研究的目的是探討常見(jiàn)的呼吸道病毒在CRS持續(xù)階段中發(fā)揮的潛在作用。 方法：53位對(duì)照組受試者,61位不伴有鼻息肉的慢性鼻-鼻竇炎(CRSsNP)患者以及67位伴有鼻息肉的慢性鼻-鼻竇炎(CRSwNP)患者被納入研究。刮取中鼻道上皮細(xì)胞以定量PCR檢測(cè)9種常見(jiàn)呼吸道病毒在各組中的數(shù)量。病人分為病毒陽(yáng)性組和病毒陰性組比較臨床癥狀數(shù)據(jù)。 結(jié)果：本實(shí)驗(yàn)檢測(cè)了鼻病毒,流感病毒A、B亞型,副流感病毒1、2、3型,呼吸道合孢病毒和冠狀病毒OC43、229E這9種常見(jiàn)呼吸道病毒。在對(duì)照組,CRSwNP及CRSsNP組中呼吸道病毒總體陽(yáng)性率分別為75.47%,68.66%和73.77%,且無(wú)統(tǒng)計(jì)學(xué)差異,三組之間單種病毒數(shù)量及多種病毒數(shù)量均無(wú)統(tǒng)計(jì)學(xué)差異。VAS評(píng)分,CT評(píng)分,鼻內(nèi)鏡評(píng)分在病毒陽(yáng)性組和病毒陰性組均無(wú)統(tǒng)計(jì)學(xué)差異。 結(jié)論：雖然常見(jiàn)的呼吸道病毒在病人中鼻道有較高的數(shù)量,但是CRSwNP及CRSsNP的持續(xù)階段相較于對(duì)照組病毒數(shù)量都沒(méi)有增加,常見(jiàn)的呼吸道病毒在CRS慢性炎癥持續(xù)過(guò)程中的具體作用機(jī)理還需要進(jìn)一步深入的研究。
[Abstract]:OBJECTIVE: Although TSLP, IL-25 and IL-33 play important roles in the initiation and development of Th2 response, their roles in the formation of Th response in eosinophilic and non-eosinophilic chronic rhinosinusitis with nasal polyps are still unknown. The correlation between the expression and the mechanism of regulation in the epithelial cells of human nasal mucosa.
METHODS: Immunohistochemistry, real-time quantitative PCR, enzyme-linked immunosorbent assay, Bio-Plex suspension chip and flow cytometry were used to detect TSLP/TSLPR/IL-7 receptor alpha (IL-7Ra), IL-25/IL-17B receptor (IL-17RB), and IL-33/membrane ST2 (ST2L)/soluble ST2 (sST2) in nasal sinus mucosa and human nasal epithelial cells. The expression of cytokines and their receptors in human nasal epithelial cells was studied by gas-liquid exchange surface culture.
Results: Compared with control group and non-eosinophilic chronic rhinosinusitis with nasal polyps, the expression of TSLP/TSLPR/lL-7Ra and STL/sST2 messenger RNA and protein in epithelial and mesenchymal cells were significantly increased, especially in epithelial cells. The expression of TSLP, TSLPR and ST2L was positively correlated with VAS score, CT score and Th2 cytokine expression in nasal sinus mucosa of eosinophilic sinusitis with nasal polyps. In addition, TSLP/TSLPR/IL-7Ra and SSTL can be induced by Th2 cytokines. However, the expressions of IL-25/IL-17RB and IL-33 can be up-regulated by Th1/Th17 cytokines, respectively. Adjust.
Conclusion: TSLP, IL-33 and their receptors form positive feedback loops and Th2 cytokines can promote the development of Th2 inflammation in eosinophilic chronic rhinosinusitis with nasal polyps.
OBJECTIVE: Respiratory tract viruses are considered to be a trigger for acute rhinosinusitis, but their role in chronic rhinosinusitis (CRS) remains unclear.
METHODS: Fifty-three control subjects, 61 patients with chronic rhinosinusitis (CRSsNP) without nasal polyps and 67 patients with chronic rhinosinusitis (CRSwNP) with nasal polyps were enrolled in the study. The negative group was compared with clinical symptom data.
Results: The total positive rates of respiratory tract viruses were 75.47%, 68.66% and 73.77% in the control group, CRSwNP and CRSsNP, respectively, and there was no statistical difference among the three groups. There was no significant difference in the number of viruses and the number of viruses. There was no significant difference in VAS score, CT score and nasal endoscopy score between the virus positive group and the virus negative group.
CONCLUSION: Although the number of common respiratory viruses in the middle nasal meatus is higher, the number of CRSwNP and CRSsNP in the persistent stage of CRS is not increased compared with that in the control group. The specific mechanism of the common respiratory viruses in the process of chronic inflammation of CRS needs further study.
【學(xué)位授予單位】：華中科技大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2015
【分類號(hào)】：R765

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