NLRP3炎性小体在鼻息肉发病中的作用与机制研究
发布时间：2018-07-13 21:18
【摘要】：目的:核苷酸结合寡聚化结构域样受体(Nucleotide-binding oligomerization domain-like receptors,NLRs)在激活和调节先天免疫反应中起关键作用。NLRP3为NLRs蛋白家族的成员,是NLRP3炎性小体的重要组成部分。近年来,NLRP3炎性小体被证实与各种疾病如哮喘,炎性肠疾病等多种炎症性疾病有关,但有关NLRP3炎性小体在鼻息肉中的作用的相关报道还较少,因此在本次研究中我们将通过研究NLRP3炎性小体及其下游因子IL-1β在鼻息肉中的表达情况,探讨NLRP3炎性小体在慢性鼻-鼻窦炎伴鼻息肉(Chronic rhinosinusitis with nasal polyp,CRSwNP)发病机制中的作用,并利用其抑制剂为CRSwNP治疗药物的开发提供新的理论依据。方法:实验共分为三组:其中鼻中隔偏曲患者的正常中鼻甲黏膜设为对照组,共15例,CRSwNP患者钩突组15例及CRSwNP患者鼻息肉组25例。蛋白免疫印迹法检测组织中NLRP3的表达情况;用RT-PCR和免疫组织化学染色(Immunohistochemistry,IHC)检测组织标本IL-1β的表达情况;在培养的鼻息肉细胞(Dispersed nasal polyp cells,DNPCs)中,利用酶联免疫吸附测定法(Enzyme linked immunosorbent assay,ELISA)检测脂多糖(Lipopolysaccharide,LPS)诱导的IL-1β的生成,并加入NLRP3炎性小体抑制剂MCC950(一种二芳基磺酰脲化合物)观察IL-1β表达的变化。所得数据采用SPSS17.0软件进行统计学分析。结果:鼻息肉组织中NLRP3的表达显著高于对照组(P0.01)。IL-1β的mRNA水平及在组织细胞中的阳性表达与对照组相比较明显增高(P0.05)。DNPCs中LPS诱导的IL-1β显著增加(P0.01),而同时给予NLRP3炎性体抑制剂组的IL-1β的表达显著降低(P0.05)。结论:NLRP3炎性小体及其下游细胞因子IL-1β在参与了 CRSwNP的发生与发展,而NLRP3炎性小体抑制剂MCC950是鼻息肉中NLRP3炎性小体介导的炎症的潜在治疗剂。
[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.
【学位授予单位】：延边大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R765
本文编号：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.
【学位授予单位】：延边大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R765
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