NLRP3炎性小體在鼻息肉發(fā)病中的作用與機(jī)制研究
發(fā)布時(shí)間：2018-07-13 21:18
【摘要】：目的:核苷酸結(jié)合寡聚化結(jié)構(gòu)域樣受體(Nucleotide-binding oligomerization domain-like receptors,NLRs)在激活和調(diào)節(jié)先天免疫反應(yīng)中起關(guān)鍵作用。NLRP3為NLRs蛋白家族的成員,是NLRP3炎性小體的重要組成部分。近年來(lái),NLRP3炎性小體被證實(shí)與各種疾病如哮喘,炎性腸疾病等多種炎癥性疾病有關(guān),但有關(guān)NLRP3炎性小體在鼻息肉中的作用的相關(guān)報(bào)道還較少,因此在本次研究中我們將通過(guò)研究NLRP3炎性小體及其下游因子IL-1β在鼻息肉中的表達(dá)情況,探討NLRP3炎性小體在慢性鼻-鼻竇炎伴鼻息肉(Chronic rhinosinusitis with nasal polyp,CRSwNP)發(fā)病機(jī)制中的作用,并利用其抑制劑為CRSwNP治療藥物的開(kāi)發(fā)提供新的理論依據(jù)。方法:實(shí)驗(yàn)共分為三組:其中鼻中隔偏曲患者的正常中鼻甲黏膜設(shè)為對(duì)照組,共15例,CRSwNP患者鉤突組15例及CRSwNP患者鼻息肉組25例。蛋白免疫印跡法檢測(cè)組織中NLRP3的表達(dá)情況;用RT-PCR和免疫組織化學(xué)染色(Immunohistochemistry,IHC)檢測(cè)組織標(biāo)本IL-1β的表達(dá)情況;在培養(yǎng)的鼻息肉細(xì)胞(Dispersed nasal polyp cells,DNPCs)中,利用酶聯(lián)免疫吸附測(cè)定法(Enzyme linked immunosorbent assay,ELISA)檢測(cè)脂多糖(Lipopolysaccharide,LPS)誘導(dǎo)的IL-1β的生成,并加入NLRP3炎性小體抑制劑MCC950(一種二芳基磺酰脲化合物)觀(guān)察IL-1β表達(dá)的變化。所得數(shù)據(jù)采用SPSS17.0軟件進(jìn)行統(tǒng)計(jì)學(xué)分析。結(jié)果:鼻息肉組織中NLRP3的表達(dá)顯著高于對(duì)照組(P0.01)。IL-1β的mRNA水平及在組織細(xì)胞中的陽(yáng)性表達(dá)與對(duì)照組相比較明顯增高(P0.05)。DNPCs中LPS誘導(dǎo)的IL-1β顯著增加(P0.01),而同時(shí)給予NLRP3炎性體抑制劑組的IL-1β的表達(dá)顯著降低(P0.05)。結(jié)論:NLRP3炎性小體及其下游細(xì)胞因子IL-1β在參與了 CRSwNP的發(fā)生與發(fā)展,而NLRP3炎性小體抑制劑MCC950是鼻息肉中NLRP3炎性小體介導(dǎo)的炎癥的潛在治療劑。
[Abstract]:Aim: nucleotide-binding oligomerization domain-like receptor (NLRs) plays a key role in the activation and regulation of innate immune response. NLRP3 is a member of NLRs protein family and an important component of NLRP3 inflammatory corpuscles. In recent years, NLRP3 inflammatory corpuscles have been proved to be associated with various diseases such as asthma, inflammatory bowel diseases and other inflammatory diseases, but there are few reports about the role of NLRP3 inflammatory corpuscles in nasal polyps. Therefore, in this study, we will study the expression of NLRP3 inflammatory corpuscles and its downstream factor IL-1 尾 in nasal polyps, and explore the role of NLRP3 inflammatory corpuscles in the pathogenesis of chronic rhinosinusitis with nasal polyps. The use of its inhibitors provides a new theoretical basis for the development of CRSwNP drugs. Methods: the experiment was divided into three groups: the normal middle turbinate mucosa of the patients with nasal septum deviation was set as control group, 15 patients with CRSwNP and 25 patients with nasal polyps were treated with CRSwNP. The expression of NLRP3 was detected by Western blot, the expression of IL-1 尾 was detected by RT-PCR and immunohistochemical staining, and the expression of IL-1 尾 was detected in cultured nasal polyp cells (DNPCs). The production of IL-1 尾 induced by lipopolysaccharide (LPS) was detected by enzyme-linked immunosorbent assay (Elisa), and the expression of IL-1 尾 was observed by adding NLRP3 inflammatory body inhibitor MCC950 (a diarylsulfonylurea compound). The data were analyzed by SPSS 17.0 software. Results: the expression of NLRP3 mRNA in nasal polyps was significantly higher than that in control group (P0.01). IL-1 尾 mRNA level and positive expression in tissue cells were significantly higher than those in control group (P0.05). LPS induced IL-1 尾 expression in DNPCs was significantly increased (P0.01), while NLRP3 inflammatory inhibition was given at the same time. The expression of IL-1 尾 in the preparation group was significantly decreased (P0.05). Conclusion the inflammatory corpuscles of NLRP3 and its downstream cytokine IL-1 尾 are involved in the genesis and development of CRSwNP. MCC950, an inflammatory corpuscle inhibitor of NLRP3, is a potential therapeutic agent for inflammation mediated by inflammatory corpuscles of NLRP3 in nasal polyps.
【學(xué)位授予單位】：延邊大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：R765
本文編號(hào)：2120772
[Abstract]:Aim: nucleotide-binding oligomerization domain-like receptor (NLRs) plays a key role in the activation and regulation of innate immune response. NLRP3 is a member of NLRs protein family and an important component of NLRP3 inflammatory corpuscles. In recent years, NLRP3 inflammatory corpuscles have been proved to be associated with various diseases such as asthma, inflammatory bowel diseases and other inflammatory diseases, but there are few reports about the role of NLRP3 inflammatory corpuscles in nasal polyps. Therefore, in this study, we will study the expression of NLRP3 inflammatory corpuscles and its downstream factor IL-1 尾 in nasal polyps, and explore the role of NLRP3 inflammatory corpuscles in the pathogenesis of chronic rhinosinusitis with nasal polyps. The use of its inhibitors provides a new theoretical basis for the development of CRSwNP drugs. Methods: the experiment was divided into three groups: the normal middle turbinate mucosa of the patients with nasal septum deviation was set as control group, 15 patients with CRSwNP and 25 patients with nasal polyps were treated with CRSwNP. The expression of NLRP3 was detected by Western blot, the expression of IL-1 尾 was detected by RT-PCR and immunohistochemical staining, and the expression of IL-1 尾 was detected in cultured nasal polyp cells (DNPCs). The production of IL-1 尾 induced by lipopolysaccharide (LPS) was detected by enzyme-linked immunosorbent assay (Elisa), and the expression of IL-1 尾 was observed by adding NLRP3 inflammatory body inhibitor MCC950 (a diarylsulfonylurea compound). The data were analyzed by SPSS 17.0 software. Results: the expression of NLRP3 mRNA in nasal polyps was significantly higher than that in control group (P0.01). IL-1 尾 mRNA level and positive expression in tissue cells were significantly higher than those in control group (P0.05). LPS induced IL-1 尾 expression in DNPCs was significantly increased (P0.01), while NLRP3 inflammatory inhibition was given at the same time. The expression of IL-1 尾 in the preparation group was significantly decreased (P0.05). Conclusion the inflammatory corpuscles of NLRP3 and its downstream cytokine IL-1 尾 are involved in the genesis and development of CRSwNP. MCC950, an inflammatory corpuscle inhibitor of NLRP3, is a potential therapeutic agent for inflammation mediated by inflammatory corpuscles of NLRP3 in nasal polyps.
【學(xué)位授予單位】：延邊大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：R765
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