【作者】 王新龙；

【导师】 赵建东；

【作者基本信息】 山东大学 ， 耳鼻咽喉科学， 2010， 硕士

【摘要】 背景：变应性鼻炎是Th2细胞及其细胞因子占优势的变态反应。Th2细胞主要合成和分泌IL-4、IL-5、IL-6、IL-10、IL-13等细胞因子。SOCS(suppressor of cytokine singnaling,细胞因子信号转导抑制因子)是近年来新发现的一类负向调节蛋白,可抑制多种细胞因子的信号通路,且大多数成员可被细胞因子和生长因子所诱导产生。其中SOCS3在Th2细胞中的表达是Th1细胞的23倍。IL-4等细胞因子能诱导SOCS3在Th2细胞上的表达,而SOCS3蛋白通过对IL-12/STAT4等通路的抑制可抑制Th1细胞及其细胞因子的产生。嗜酸性粒细胞增多是变应性鼻炎主要病理表现之一,Eotaxin-2为嗜酸性粒细胞趋化因子之一。Eotaxin-2(CCL24)与Eotaxin-1(CCL11) Eotaxin-3(CCL26)同属于趋化因子CC亚家族成员,他们均选择性的专一的与其共同的受体CCR3结合进而趋化并激活嗜酸性粒细胞。三种趋化因子的生物学作用相似,与嗜酸性粒细胞表面的受体CCR3结合后可促使嗜酸性粒细胞合成LTC4、产生活性氧簇、脱颗粒释放炎性介质等从而发挥其效应器功能。研究发现在鼻息肉患者和哮喘患者中,IL-4、IL-13等细胞因子能诱导鼻黏膜和支气管黏膜单核细胞、上皮细胞等表达Eotaxin-2增多,其中IL-4诱导鼻黏膜和支气管黏膜表达Eotaxin-2能力较强。目的：本实验通过应用免疫组化技术研究SOCS3及Eotaxin-2在变态反应性鼻炎鼻粘膜中的表达,通过二者相关性,分析SOCS3对Eotaxin-2的影响,进一步探讨SOCS3在变态反应性鼻炎发病机制中的作用及对临床症状的影响。方法：按照2004年兰州会议关于变态反应性鼻炎的诊断标准,选取20例AR患者鼻粘膜为实验组和15例单纯鼻中隔偏曲患者鼻粘膜为对照组,应用免疫组织化学技术分别检测SOCS3及Eotaxin-2的表达,结果以(x±s)表示,组间差异性比较用t检验,并用直线相关分析法对SOCS3及Eotaxin-2表达的相关性进行分析。结果：在AR患者鼻黏膜中,SOCS3及Eotaxin-2的表达上调,在鼻黏膜炎性细胞、上皮细胞、腺体细胞、血管内皮细胞呈显著性表达。平均光密度值SOCS3为0.2401±0.01463, Eotaxin-2为0.2398±0.01423,与对照组相比,均P<0.01,差异有统计学意义。AR患者鼻黏膜中SOCS3及Eotaxin-2的表达具相关性(r=0.951,P<0.01)。结论：AR患者SOCS3及Eotaxin-2在鼻黏膜组织中表达增高,且二者呈正相关。此结果可能由于SOCS3增强Th2细胞反应,间接导致Eotaxin-2增多。也可能是SOCS3与Eotaxin-2直接相互诱导所致。确切机制有待进一步研究。更多还原

【Abstract】 Background:Th2 cells and their cytokines is dominant in allergic rhinitis. Th2 cells synthesize and secrete mainly IL-4, IL-5, IL-6, IL-10, IL-13 and other cytokines. SOCS (suppressor of cytokine singnaling) is a class of negative regulatory proteins had been discovered recently, can inhibit a variety of cytokine signal pathway, and the majority of the members can be induced by cytokines and growth factors. SOCS3 in Th2 cells is 23 times more than in Thl cells. IL-4 and other cytokines can induce SOCS3 expression in Th2 cells.SOCS3 protein can decrease Thl cells and their cytokine through inhibiting IL-12/STAT4 pathways.An increase in Eosinophils is a major pathological manifestations of allergic rhinitis, Eotaxin-2 is one of the Eosinophil Chemotactic Factors. Eotaxin-2 (CCL24) as well as Eotaxin-1 (CCL11), Eotaxin-3 (CCL26) belongs to the CC chemokine subfamily members. They only combine with their common receptor CCR3 in order to attract and activate Eosinophils. They play similar biological roles. After combining with the eosinophil cell surface receptors CCR3,they can promote Eosinophils to synthesize LTC4, generate reactive oxygen species, degranulation and release inflammatory mediators, and so on, to play its effector function.Study shows that in nasal polyps patients and Asthma patients, IL-4, IL-13 and so on could induce Mononuclear cells and Epithelial cells of nasal mucosa and bronchus mucosa increasing the expression of Eotaxin-2, in which IL-4 play more important role.Objective:In this research, immunohistochemisty was performed to study the expression of SOCS3 and Eotaxin-2 in allergic rhinitis nasal mucosa. By analyzing the correlation between SOCS3 and Eotaxin-2, we try to know the importance of the SOCS3 in allergic rhinitis pathogenesis and its effects on clinical symptoms. Methods:According to the diagnostic criteria revised by 2004 Lanzhou meeting on allergic rhinitis, twenty cases of allergic rhinitis nasal mucosa tissues were collected as experimental groups and fifteen cases of deviation of nasal septum nasal mucosa tissues as control. Immunohistochemisty was performed to detect the expression of SOCS3 and Eotaxin-2 respectively. The experimental date was expessed with x±s and the comparison of difference between the groups was detected by t-test. The linear correlation analysis method was used to analyze the relationship between SOCS3 and Eotaxin-2 expression.Results:SOCS3 and Eotaxin-2 expression were both increased in the AR patients. There were positive staining not only in inflammatory cells and vascular endothelial cells but also in epithelial cells and glandular epithelium cells, compared with control group. The expression of SOCS3 (0.2401±0.01463) and Eotaxin-2 (0.2398±0.01423) were significantly higher than that in control group (P＜0.01). The difference was statistically significant. The SOCS3 expression was closely related to Eotaxin-2 expression(r=0.951, P＜0.01).Conclusions:The increased expression of SOCS3 and Eotaxin-2 in allergic rhinitis is well evidenced. SOCS3 shows positive correlation with Eotaxin-2. This result may be due to SOCS3 enhanced Th2 cell response, indirectly leading to an increase in Eotaxin-2. SOCS3 may also be a direct correlation with Eotaxin-2 by inducing with each other. The exact mechanism remains to be further studied.更多还原