白三烯受體拮抗劑對變應性鼻炎大鼠鼻黏膜炎癥和重塑影響的研究
發(fā)布時間：2019-05-20 13:32
【摘要】： 目的：通過變應性鼻炎模型IL-25與IL-12水平和NF-κB, MMP-9在鼻黏膜重塑表達檢測,探討它們在變應性鼻炎發(fā)病機制作用,為臨床提供新的理論依據(jù)。觀察給予白三烯受體拮抗劑-孟魯斯特干預后,變應性鼻炎大鼠鼻粘膜NF-κB, MMP-9表達,和外周血清中IL-25與IL-12水平變化,探討白三烯受體拮抗在變應性鼻炎炎癥和重塑的應用價值,并為治療變應性鼻炎的藥物研發(fā)提供新思路。 方法：選30只健康的SD大鼠隨機分為三組,A組：孟魯斯特組(SD大鼠10只),B組：變應性鼻炎組(SD大鼠10只),C組：正常對照組(SD大鼠10只)。首先對B組變應性鼻炎組大鼠予以卵清白蛋白進行基礎致敏、致敏加強、局部激發(fā)建立變應性鼻炎動物模型,C組正常對照組則以等量生理鹽水代替進行腹腔注射及滴鼻。A組：孟魯斯特組在每次的局部激發(fā)后給予孟魯斯特治療,方法為：按6mg/Kg. bid孟魯斯特給予每只大鼠灌胃治療。應用酶聯(lián)免疫吸附法(ELISE法)檢測三組大鼠外周血清IL-25與IL-12水平。應用免疫組化法檢測三組大鼠鼻黏膜NF-κB和MMP-9的表達。采用SPSS13.0統(tǒng)計軟件進行數(shù)據(jù)分析,運用單因素方差分析(兩組的差異性比較采用t檢驗)及直線回歸相關分析的統(tǒng)計學方法處理數(shù)據(jù)。所得數(shù)據(jù)以均數(shù)±標準差(x±S)表示,以P0.05為顯著性界限。 結果： 1變應性鼻炎組大鼠動物模型建立成功,均表現(xiàn)出明顯的抓鼻、噴嚏及流涕等癥狀。 2血清IL-25水平(pg/ml):10例AR大鼠血清中,IL-25的含量為(37.7±2.7) pg/ml;10例對照組大鼠血清中,IL-25的含量為(26.2±1.9)pg/ml;10例治療組大鼠血清中,IL-25的含量為(32.8±4.6) pg/ml;經(jīng)統(tǒng)計學檢驗,進行組間比較：三組間比較差異有顯著性意義(P0.05)。 3血清IL-12水平(pg/ml):10例AR大鼠血清中,IL-12的含量為(26.1±0.6)pg/ml；10例對照組大鼠血清中,IL-12的含量為(36.2±1.4)pg/mpl；10例治療組大鼠血清中,IL-12的含量為(32.5±0.9)pg/ml；經(jīng)統(tǒng)計學檢驗,進行組間比較：三組間比較差異有顯著性意義(P0.05)。 4在AR大鼠血清中IL-25與IL-12兩者之間呈直線負相關,相關系數(shù)r=-0.685(P0.01)。 5變應性鼻炎鼻黏膜可發(fā)生黏膜重塑現(xiàn)像,NF-κB p65的陽性信號主要位于上皮細胞、腺體細胞和一些炎性細胞中,胞漿、胞核均著色,呈棕黃色。AR組鼻黏膜中NF-κB p65陽性信號(OD值為0.3613±0.0276)與其他二組比較強度最強(P0.001)；治療的陽性信號(OD值為0.2366±0.0183)強度較AR組組弱,但與正常對照組比較(OD值為0.1500±0.0225),陽性信號強(P0.001)。 6 MMP-9主要表達在黏膜上皮細胞及固有層內浸潤的炎細胞胞漿,為棕黃色顆粒。AR組鼻黏膜中,MMP-9的陽性信號(OD值為0.2479±0.0254)與其他二組比較強度最強(P0.001)；治療組陽性信號(OD值為(0.1795±0.0250)強度較AR組弱,但與對照組(OD值為0.1186±0.0252)比較,陽性信號強(P0.001)。 7在AR大鼠鼻黏膜中NF-κB p65和MMP-9兩者之間呈直線正相關,相關系數(shù)r=0.879(P0.01)。 結論： 1以卵清白蛋白為變應原,通過對大SD大鼠進行基礎致敏、致敏加強及局部激發(fā)可成功建立既能反應變應性鼻炎典型癥狀,又能反應相關病理變化(重塑)變應性鼻炎大鼠實驗動物模型。 2變應性鼻炎模型組血清IL-25水平明顯升高,提示IL-25參與了變應性鼻炎的發(fā)病,在變應性鼻炎中起到了促進炎癥發(fā)展的作用。變應性鼻炎模型組血清IL-12濃度明顯低于正常對照組,與IL-25呈負相關關系,說明在變應性鼻炎的發(fā)病存在有Thl細胞功能減低和Th2細胞功能亢進的Th1/Th2細胞因子的失衡。 3變應性鼻炎鼻黏膜可發(fā)生黏膜重塑現(xiàn)像,變應性鼻炎模型組NF-κB65和MMP-9表達均呈陽性或強陽性,這說明NF-κB和MMP-9參與了變應性鼻炎鼻黏膜內組織重塑特征的改變。 4給于白三烯受體拮抗劑后,治療組中IL-25水平水平降低并接近正常對照組,治療組中IL-12水平升高并接近正常對照組。說明白三烯受體拮抗劑可以通過調節(jié)TH1/TH2細胞因子的分化來發(fā)揮其抗炎作用。 5給于白三烯受體拮抗劑后,治療組中NF-κB和MMP-9陽性表達均下調,這說明早期應用抗變態(tài)反應藥物孟魯斯特不僅能夠抑制抗原攻擊引起的變應性炎癥同時還能有效抑制鼻黏膜的組織重塑。
[Abstract]:Objective: To study the expression of IL-25 and IL-12 and the expression of NF-B and MMP-9 in the nasal mucosa, and to provide a new theoretical basis for clinical application. The effects of leukotriene receptor antagonist on inflammation and remodeling of allergic rhinitis were discussed in the study of the expression of NF-B, MMP-9 and the level of IL-25 and IL-12 in the peripheral blood of allergic rhinitis rats following the administration of leukotriene receptor antagonist-Menutest intervention. And provides a new thought for the research and development of the medicine for treating allergic rhinitis. Methods: Thirty healthy SD rats were randomly divided into three groups: group A: Montelustgroup (10 SD rats), group B: allergic rhinitis group (10 SD rats), group C: normal control group (SD rat 1). 0). First of all, the rats of the group B allergic rhinitis group were sensitized with ovalbumin, the sensitization was enhanced, the model of allergic rhinitis was established by local excitation, and the normal control group in group C was replaced by the same amount of normal saline instead of the abdominal cavity injection. and nasal drop. Group A: The Menutest group was treated with Montelustast after each local excitation, and the method was as follows: according to 6 mg / Kg. bid Menutest to give each rat Detection of IL-25 and IL-1 in peripheral blood of three groups of rats by enzyme-linked immunosorbent assay (ELISE) 2. The expression of NF-B and MMP-9 in the nasal mucosa of three groups was detected by immunohistochemistry. The expression of SPSS13.0 statistical software was used for data analysis, and a single-factor analysis of variance (the difference between the two groups was compared with t-test) and the statistical method of linear regression correlation analysis. The obtained data was expressed by mean square standard deviation (x-S), which was marked by the mean standard deviation (x-S). sex limit Results: The model of the rat model of the allergic rhinitis group was found to be successful. The levels of IL-25 in the serum of 10 patients with AR were (37.7% and 2.7) pg/ ml, and the content of IL-25 was (26.2% 1.9) pg/ ml in 10 cases of control group, and the content of IL-25 in 10 treated rats was (32.8%). .6) pg/ ml; comparison between groups by statistical test: comparison of three groups The level of IL-12 in serum of 10 patients with AR was (26.1%) pg/ ml, and the content of IL-12 was (36.2% 1.4) pg/ mpl in 10 cases of control group, and the content of IL-12 in 10 treated rats was (32). .5 (0.9) pg/ ml; compared between groups by statistical test:3 The difference of IL-25 and IL-12 in the serum of AR rats was significant (P0.05). The correlation coefficient r =-0.685 (P0.01). The mucosal remodeling of the nasal mucosa of the allergic rhinitis and the positive signal of NF-B p65 were mainly located in the epithelial cells. The positive signal (OD value of 0.3613-0.0276) in the nasal mucosa of AR group was stronger than that of other two groups (P 0.001). The positive signal (OD value of 0.2366-0.0183) in the treatment was lower than that of the AR group, but compared with the normal control group (OD value of 0. .1500 (0.0225), positive signal (P0.001). 6MMP-9 In the nasal mucosa of AR group, the positive signal (OD value of 0.2479-0.0254) in the nasal mucosa of AR group and the other two groups was the strongest (P0.001); the positive signal (OD value of 0.1795-0.0250) in the treatment group was weaker than that of the AR group, but compared with the control group (OD value The positive signal was strong (P0.001) compared with 0.1186 (0.0252). 鍜孧M The relationship between P-9 and P-9 was positive correlation, and the correlation coefficient was r = 0.879 (P0.01). Conclusion:1 The ovalbumin is the allergen, and the primary sensitization, sensitization and local excitation of the large SD rats can be successful. In that experimental animal model of rat with allergic rhinitis, a typical symptom of allergic rhinitis was established, and the serum IL-2 in the allergic rhinitis model group was established. The level of IL-12 in the allergic rhinitis model group was significantly lower than that of the control group, and the level of IL-12 in the allergic rhinitis model group was significantly lower than that of the control group. The imbalance of Th1/ Th2 cytokines in the pathogenesis of allergic rhinitis is the imbalance of the Th1/ Th2 cytokines in the reduction of the function of the Thl cells and the hyperfunction of the Th2 cells. The expression of MMP-9 was positive or positive, suggesting that NF-B and MMP-9 were involved in the change of the remodeling of the tissue remodeling in the nasal mucosa of allergic rhinitis. After the leukotriene receptor antagonist, the level of IL-25 in the treatment group was reduced and was close to the normal control group, in the treatment group I The level of L-12 is elevated and is close to the normal control group. It is indicated that the leukotriene receptor antagonist can play its anti-inflammatory effect by regulating the differentiation of the TH1/ TH2 cytokine.
【學位授予單位】：河北醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2010
【分類號】：R765.21
本文編號：2481679
[Abstract]:Objective: To study the expression of IL-25 and IL-12 and the expression of NF-B and MMP-9 in the nasal mucosa, and to provide a new theoretical basis for clinical application. The effects of leukotriene receptor antagonist on inflammation and remodeling of allergic rhinitis were discussed in the study of the expression of NF-B, MMP-9 and the level of IL-25 and IL-12 in the peripheral blood of allergic rhinitis rats following the administration of leukotriene receptor antagonist-Menutest intervention. And provides a new thought for the research and development of the medicine for treating allergic rhinitis. Methods: Thirty healthy SD rats were randomly divided into three groups: group A: Montelustgroup (10 SD rats), group B: allergic rhinitis group (10 SD rats), group C: normal control group (SD rat 1). 0). First of all, the rats of the group B allergic rhinitis group were sensitized with ovalbumin, the sensitization was enhanced, the model of allergic rhinitis was established by local excitation, and the normal control group in group C was replaced by the same amount of normal saline instead of the abdominal cavity injection. and nasal drop. Group A: The Menutest group was treated with Montelustast after each local excitation, and the method was as follows: according to 6 mg / Kg. bid Menutest to give each rat Detection of IL-25 and IL-1 in peripheral blood of three groups of rats by enzyme-linked immunosorbent assay (ELISE) 2. The expression of NF-B and MMP-9 in the nasal mucosa of three groups was detected by immunohistochemistry. The expression of SPSS13.0 statistical software was used for data analysis, and a single-factor analysis of variance (the difference between the two groups was compared with t-test) and the statistical method of linear regression correlation analysis. The obtained data was expressed by mean square standard deviation (x-S), which was marked by the mean standard deviation (x-S). sex limit Results: The model of the rat model of the allergic rhinitis group was found to be successful. The levels of IL-25 in the serum of 10 patients with AR were (37.7% and 2.7) pg/ ml, and the content of IL-25 was (26.2% 1.9) pg/ ml in 10 cases of control group, and the content of IL-25 in 10 treated rats was (32.8%). .6) pg/ ml; comparison between groups by statistical test: comparison of three groups The level of IL-12 in serum of 10 patients with AR was (26.1%) pg/ ml, and the content of IL-12 was (36.2% 1.4) pg/ mpl in 10 cases of control group, and the content of IL-12 in 10 treated rats was (32). .5 (0.9) pg/ ml; compared between groups by statistical test:3 The difference of IL-25 and IL-12 in the serum of AR rats was significant (P0.05). The correlation coefficient r =-0.685 (P0.01). The mucosal remodeling of the nasal mucosa of the allergic rhinitis and the positive signal of NF-B p65 were mainly located in the epithelial cells. The positive signal (OD value of 0.3613-0.0276) in the nasal mucosa of AR group was stronger than that of other two groups (P 0.001). The positive signal (OD value of 0.2366-0.0183) in the treatment was lower than that of the AR group, but compared with the normal control group (OD value of 0. .1500 (0.0225), positive signal (P0.001). 6MMP-9 In the nasal mucosa of AR group, the positive signal (OD value of 0.2479-0.0254) in the nasal mucosa of AR group and the other two groups was the strongest (P0.001); the positive signal (OD value of 0.1795-0.0250) in the treatment group was weaker than that of the AR group, but compared with the control group (OD value The positive signal was strong (P0.001) compared with 0.1186 (0.0252). 鍜孧M The relationship between P-9 and P-9 was positive correlation, and the correlation coefficient was r = 0.879 (P0.01). Conclusion:1 The ovalbumin is the allergen, and the primary sensitization, sensitization and local excitation of the large SD rats can be successful. In that experimental animal model of rat with allergic rhinitis, a typical symptom of allergic rhinitis was established, and the serum IL-2 in the allergic rhinitis model group was established. The level of IL-12 in the allergic rhinitis model group was significantly lower than that of the control group, and the level of IL-12 in the allergic rhinitis model group was significantly lower than that of the control group. The imbalance of Th1/ Th2 cytokines in the pathogenesis of allergic rhinitis is the imbalance of the Th1/ Th2 cytokines in the reduction of the function of the Thl cells and the hyperfunction of the Th2 cells. The expression of MMP-9 was positive or positive, suggesting that NF-B and MMP-9 were involved in the change of the remodeling of the tissue remodeling in the nasal mucosa of allergic rhinitis. After the leukotriene receptor antagonist, the level of IL-25 in the treatment group was reduced and was close to the normal control group, in the treatment group I The level of L-12 is elevated and is close to the normal control group. It is indicated that the leukotriene receptor antagonist can play its anti-inflammatory effect by regulating the differentiation of the TH1/ TH2 cytokine.
【學位授予單位】：河北醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2010
【分類號】：R765.21
【引證文獻】
相關碩士學位論文 前1條
1 汝海婧;鼻鼽散治療常年性變應性鼻炎的臨床療效觀察[D];黑龍江中醫(yī)藥大學;2011年
，本文編號：2481679
本文鏈接：http://sikaile.net/yixuelunwen/yank/2481679.html
最近更新
教材專著
