Loading...
|
Please use this identifier to cite or link to this item:
https://ir.csmu.edu.tw:8080/ir/handle/310902500/10344
|
| Title: | 金針菇免疫調節蛋白FIP-fve 對氣喘小鼠體內免疫環境、IL-22與IL-17的影響
The Role of FIP-fve Affect IL-22, IL-17 and Immune Environment in Asthma Animal Model |
| Authors: | 呂克桓 |
| Contributors: | 醫學系 |
| Keywords: | FIP-fve;AHR;呼吸道重塑;IL-22;IL-17;慢性呼吸道發炎
FIP-fve;AHR;airway remodeling;IL-22,IL-17;chronic airway inflammation |
| Date: | 2014 |
| Issue Date: | 2015-02-25T09:18:50Z (UTC)
|
| Abstract: | 在過去二十年間，氣喘疾病的發生率持續快速增加中。隨著越來越多人投入氣喘的研究， 應用於治療過敏氣喘疾病的新藥劑因此不斷被開發出來。話雖如此，但目前已知的藥物僅能提 供疾病症狀的部分舒解。因此往後的目標仍需藉由瞭解其複雜的機制，以開發更多具功效的藥 物來遏止氣喘的發炎反應產生，甚至更進一步可以回復已損傷重塑過的肺組織。目前的研究發 現，白三醯素對於整個氣喘的病理變化佔有重要的角色。另外也有些研究發現一些中草藥及食 物的萃取物，對於抑制氣喘氣道重塑的過程，具有調控輔助的功能。 根據研究團隊先前已發表之研究證實，金針菇免疫調節蛋白 FIP（fungal immunomodulatory peptide）-fve 對於致敏小鼠呼吸道之發炎反應具有顯著的抑制作用，不僅能減緩呼吸道過度反 應現象(AHR)，亦能使致敏小鼠體內 Th2 細胞激素分泌減少，並且顯著減少致敏現象標的細胞 Eosinophils之產生。於本次研究更加深入探討於發炎與致敏體內之免疫微環境中，FIP-fve究竟 是透過何種機制影響整體免疫反應，此研究將探討 FIP-fve在各種介白質 RNA層級中之表現差 異，並且探討其於 Th1、Th2、Treg、Th17以及 Th22免疫細胞中之各種反應與影響以完整描繪 出 FIP-fve在致敏反應中對急性發炎與慢性發炎之分子傳遞機制與相關影響。 本研究中，我們將 BALB/C的母鼠，經過第 0天與第 14天的腹腔注射蛋清蛋白以及第 14 天與第 25-27 天給予經鼻的蛋清蛋白後，氣喘模組將會建立成功。我們隨機選擇致敏的老鼠， 依照實驗時程分組的不同，分別於氣喘模組建立過程的第 0天至第 14天，或是呼吸道發炎組建 立過程的第 14天至第 27天，以餵食針餵食 FIP- fve或MK(montelukast)。此外，研究中更納入 慢性期之研究，將實驗氣喘模組轉為 104天慢性致敏流程並於實驗進程的第 69至 73天給予經 鼻的蛋清蛋白後建立慢性氣喘模組。另外目前已知具有抗發炎效果，且廣泛應用於臨床的類固 醇，也將會選擇一組致敏之老鼠於上述時程給予餵食，當作治療成效的參考指標。 依據最近我們初步研究得知，確定 FIP- fve 在老鼠的氣喘模組中，無論是急性期或慢性期 具有顯著治療的效果外且 FIP-fve對於呼吸道膠原蛋白沈積似乎亦具有減緩的效果，因此藉由此 一模式進行深入探討，FIP-fve 對於致敏小鼠的分子傳遞機制以及對於體內免疫微環境與 IL-17，IL-22之影響，並且納入臨床藥物 montelukast作比較，以徹底了解兩者藥物間之差異與 分子相關機制的不同性，以為發炎與致敏疾病找尋更完善的治療與預防方式。
The incidence of asthma has increased substantially in the last two decades. New medication is developed rapidly in recent years to apply to allergic asthma, since lots of people have investigated about these. However, now existing drugs just offer partial relief of symptoms in such disease. The goal of feature is to understand the complicated mechanism of asthma, and develop more effective drugs for suppressing the inflammatory response in asthma. Even we can then reverse the damaged lung tissue after airway remodeling. As we known today, asthma is a repeated chronic inflammatory disease. It is characterized by a complex response of pulmonary eosinophilia, edema, mucus hypersecretion, and airway hyperreactivity (AHR). Under the condition of long-term asthma, airway remodeling may develop by increased goblet cells, subepithelial fibrosis, airway smooth muscle mass increased and vascular hyperplasia. These make asthma control more difficult. According to recent research about asthma, leukotriene got important role in whole pathologic change of asthma. Our previous data show that fungal immunomodulatory peptide-fve (FIP-fve) could suppress AHR response, induced Th1 and Treg cytokine, and reduced Th2 cytokine, and in our preliminary result also show that FIP-fve could reduce collagen precipitation. We would examine the role of FIP-fve and compare leukotriene receptor antagonist (montelukast) in a mouse asthma model after allergen-induced acute and chronic lung inflammation and airway remodeling. Female BALB/c mice, after intraperitoneal ovalbumin sensitization on Days 0 and 14, received intranasal OVA on Days14 and Days 25-27. The mouse asthma model was set up. The sensitized mice were divided into different group according to the course of designed airway change. Different groups of sensitized mice received FIP-fve, Montelukast (leukotriene receptor antagonist) or combination or corticosteroid via intragastric feeding on Day 0-14. The other groups of sensitized mice received same drugs on Day 14-27. Moreover, the chronic stage in this asthma animal model was received intranasal OVA on Days 69-73 and the chronic model was set up. We will also evaluate the effect of FIP-fve, Montelukast or both combination in this chronic asthma mouse model. In this experiment, we will further evaluate the effect of FIP-fve on Th17 and Th22 and evaluate the molecule environment and signal transduction of FIP-fve and montelukast on asthma treatment. According to those objects we will detect RNA levels of interleukins and analysis with Th1, Th2, Treg, Th17and Th22 immune cells. |
| URI: | https://ir.csmu.edu.tw:8080/ir/handle/310902500/10344 |
| Appears in Collections: | [醫學研究所] 研究計劃
|
Files in This Item:
There are no files associated with this item.
|
All items in CSMUIR are protected by copyright, with all rights reserved.
|
