本文選題：中耳炎 + PGRN��； 參考：《重慶醫(yī)科大學》2017年碩士論文

【摘要】：目的:急性中耳炎(AOM)患者多為兒童,在發(fā)達國家約80%以上的三歲前兒童都曾患過中耳炎。顆粒蛋白前體(progranulin,PGRN)是一種多功能的生長因子,廣泛表達于各種組織和細胞。PGRN在胚胎發(fā)育、傷口修復、腫瘤發(fā)生等生理及病理過程中均發(fā)揮有重要作用。近年來,研究表明PGRN與TNFR結(jié)合參與炎癥疾病的發(fā)展,將PGRN與TNF-α結(jié)合,為PGRN生物活性、炎癥及自身免疫性疾病研究提供了新思路。但關于PGRN在中耳炎中的作用及其機制尚未見相關報道。方法:采用聽泡穿刺法建立C56BL/6野生小鼠和PGRN缺陷小鼠急性中耳炎模型。中耳組織石蠟切片經(jīng)免疫組織化學染色和HE染色,觀察小鼠中耳PGRN表達和中耳組織損傷程度。收集中耳灌洗液,計數(shù)小鼠中耳炎癥細胞和細菌載量,流式細胞分類計數(shù)中性粒細胞與巨噬細胞比例,ELISA檢測炎癥因子和趨化因子的表達。結(jié)果:小鼠感染S.pn后中耳PGRN表達水平明顯升高。與WT小鼠相比,PGRN-/-小鼠炎癥細胞募集增多,細菌載量增加,炎癥因子和趨化因子表達也明顯提高,其中CCL2最為顯著,促進巨噬細胞募集。使用PGRN重組蛋白可明顯提高PGRN-/-小鼠細菌清除能力,抑制炎癥反應。結(jié)論:本研究證實PGRN可通過抑制CCL2表達,降低巨噬細胞在中耳腔募集,減輕中耳炎癥反應。
[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- 偽 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.
【學位授予單位】：重慶醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R764.21

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