急性中耳炎中PGRN通过下调CCL2表达抑制巨噬细胞募集减轻炎症反应

发布时间：2018-05-09 22:23

本文选题：中耳炎 + PGRN　；参考：《重庆医科大学》2017年硕士论文

【摘要】：目的:急性中耳炎(AOM)患者多为儿童,在发达国家约80%以上的三岁前儿童都曾患过中耳炎。颗粒蛋白前体(progranulin,PGRN)是一种多功能的生长因子,广泛表达于各种组织和细胞。PGRN在胚胎发育、伤口修复、肿瘤发生等生理及病理过程中均发挥有重要作用。近年来,研究表明PGRN与TNFR结合参与炎症疾病的发展,将PGRN与TNF-α结合,为PGRN生物活性、炎症及自身免疫性疾病研究提供了新思路。但关于PGRN在中耳炎中的作用及其机制尚未见相关报道。方法:采用听泡穿刺法建立C56BL/6野生小鼠和PGRN缺陷小鼠急性中耳炎模型。中耳组织石蜡切片经免疫组织化学染色和HE染色,观察小鼠中耳PGRN表达和中耳组织损伤程度。收集中耳灌洗液,计数小鼠中耳炎症细胞和细菌载量,流式细胞分类计数中性粒细胞与巨噬细胞比例,ELISA检测炎症因子和趋化因子的表达。结果:小鼠感染S.pn后中耳PGRN表达水平明显升高。与WT小鼠相比,PGRN-/-小鼠炎症细胞募集增多,细菌载量增加,炎症因子和趋化因子表达也明显提高,其中CCL2最为显著,促进巨噬细胞募集。使用PGRN重组蛋白可明显提高PGRN-/-小鼠细菌清除能力,抑制炎症反应。结论:本研究证实PGRN可通过抑制CCL2表达,降低巨噬细胞在中耳腔募集,减轻中耳炎症反应。
[Abstract]:Objective: most patients with acute otitis media (AOM) are children. More than 80% of the children in developed countries have had otitis media before the age of 3 years. Progranulinus granulinus (PGRN), a multifunctional growth factor, is widely expressed in various tissues and cells. PGRN plays an important role in embryonic development, wound repair, tumorigenesis and other physiological and pathological processes. In recent years, it has been shown that the combination of PGRN and TNFR is involved in the development of inflammatory diseases. The combination of PGRN and TNF- 伪 provides a new idea for the study of PGRN biological activity, inflammation and autoimmune diseases. However, the role of PGRN in otitis media and its mechanism have not been reported. Methods: acute otitis media models of C56BL/6 wild mice and PGRN deficient mice were established by auditory bubble puncture. The expression of PGRN and the degree of middle ear injury were observed by immunohistochemical staining and HE staining in paraffin sections of middle ear tissue of mice. The middle ear lavage fluid was collected and the inflammatory cells and bacterial loads in the middle ear of mice were counted. The ratio of neutrophils to macrophages was counted by flow cytometry. The expression of inflammatory factors and chemokines was detected by Elisa. Results: the expression of PGRN in middle ear of mice infected with S.pn was significantly increased. Compared with WT mice, the number of inflammatory cells increased, the bacterial load increased, and the expression of inflammatory factors and chemokines in WT mice was increased, and CCL2 was the most significant in promoting macrophage recruitment. The use of PGRN recombinant protein could significantly improve bacterial clearance and inhibit inflammatory response in PGRN-r-mice. Conclusion: PGRN can inhibit the expression of CCL2, reduce the recruitment of macrophages in the middle ear cavity and alleviate the inflammation of the middle ear.
【学位授予单位】：重庆医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R764.21

【参考文献】