白三烯受体拮抗剂对变应性鼻炎大鼠鼻黏膜炎症和重塑影响的研究
发布时间：2019-05-20 13:32
【摘要】： 目的：通过变应性鼻炎模型IL-25与IL-12水平和NF-κB, MMP-9在鼻黏膜重塑表达检测,探讨它们在变应性鼻炎发病机制作用,为临床提供新的理论依据。观察给予白三烯受体拮抗剂-孟鲁斯特干预后,变应性鼻炎大鼠鼻粘膜NF-κB, MMP-9表达,和外周血清中IL-25与IL-12水平变化,探讨白三烯受体拮抗在变应性鼻炎炎症和重塑的应用价值,并为治疗变应性鼻炎的药物研发提供新思路。 方法：选30只健康的SD大鼠随机分为三组,A组：孟鲁斯特组(SD大鼠10只),B组：变应性鼻炎组(SD大鼠10只),C组：正常对照组(SD大鼠10只)。首先对B组变应性鼻炎组大鼠予以卵清白蛋白进行基础致敏、致敏加强、局部激发建立变应性鼻炎动物模型,C组正常对照组则以等量生理盐水代替进行腹腔注射及滴鼻。A组：孟鲁斯特组在每次的局部激发后给予孟鲁斯特治疗,方法为：按6mg/Kg. bid孟鲁斯特给予每只大鼠灌胃治疗。应用酶联免疫吸附法(ELISE法)检测三组大鼠外周血清IL-25与IL-12水平。应用免疫组化法检测三组大鼠鼻黏膜NF-κB和MMP-9的表达。采用SPSS13.0统计软件进行数据分析,运用单因素方差分析(两组的差异性比较采用t检验)及直线回归相关分析的统计学方法处理数据。所得数据以均数±标准差(x±S)表示,以P0.05为显著性界限。 结果： 1变应性鼻炎组大鼠动物模型建立成功,均表现出明显的抓鼻、喷嚏及流涕等症状。 2血清IL-25水平(pg/ml):10例AR大鼠血清中,IL-25的含量为(37.7±2.7) pg/ml;10例对照组大鼠血清中,IL-25的含量为(26.2±1.9)pg/ml;10例治疗组大鼠血清中,IL-25的含量为(32.8±4.6) pg/ml;经统计学检验,进行组间比较：三组间比较差异有显著性意义(P0.05)。 3血清IL-12水平(pg/ml):10例AR大鼠血清中,IL-12的含量为(26.1±0.6)pg/ml；10例对照组大鼠血清中,IL-12的含量为(36.2±1.4)pg/mpl；10例治疗组大鼠血清中,IL-12的含量为(32.5±0.9)pg/ml；经统计学检验,进行组间比较：三组间比较差异有显著性意义(P0.05)。 4在AR大鼠血清中IL-25与IL-12两者之间呈直线负相关,相关系数r=-0.685(P0.01)。 5变应性鼻炎鼻黏膜可发生黏膜重塑现像,NF-κB p65的阳性信号主要位于上皮细胞、腺体细胞和一些炎性细胞中,胞浆、胞核均着色,呈棕黄色。AR组鼻黏膜中NF-κB p65阳性信号(OD值为0.3613±0.0276)与其他二组比较强度最强(P0.001)；治疗的阳性信号(OD值为0.2366±0.0183)强度较AR组组弱,但与正常对照组比较(OD值为0.1500±0.0225),阳性信号强(P0.001)。 6 MMP-9主要表达在黏膜上皮细胞及固有层内浸润的炎细胞胞浆,为棕黄色颗粒。AR组鼻黏膜中,MMP-9的阳性信号(OD值为0.2479±0.0254)与其他二组比较强度最强(P0.001)；治疗组阳性信号(OD值为(0.1795±0.0250)强度较AR组弱,但与对照组(OD值为0.1186±0.0252)比较,阳性信号强(P0.001)。 7在AR大鼠鼻黏膜中NF-κB p65和MMP-9两者之间呈直线正相关,相关系数r=0.879(P0.01)。 结论： 1以卵清白蛋白为变应原,通过对大SD大鼠进行基础致敏、致敏加强及局部激发可成功建立既能反应变应性鼻炎典型症状,又能反应相关病理变化(重塑)变应性鼻炎大鼠实验动物模型。 2变应性鼻炎模型组血清IL-25水平明显升高,提示IL-25参与了变应性鼻炎的发病,在变应性鼻炎中起到了促进炎症发展的作用。变应性鼻炎模型组血清IL-12浓度明显低于正常对照组,与IL-25呈负相关关系,说明在变应性鼻炎的发病存在有Thl细胞功能减低和Th2细胞功能亢进的Th1/Th2细胞因子的失衡。 3变应性鼻炎鼻黏膜可发生黏膜重塑现像,变应性鼻炎模型组NF-κB65和MMP-9表达均呈阳性或强阳性,这说明NF-κB和MMP-9参与了变应性鼻炎鼻黏膜内组织重塑特征的改变。 4给于白三烯受体拮抗剂后,治疗组中IL-25水平水平降低并接近正常对照组,治疗组中IL-12水平升高并接近正常对照组。说明白三烯受体拮抗剂可以通过调节TH1/TH2细胞因子的分化来发挥其抗炎作用。 5给于白三烯受体拮抗剂后,治疗组中NF-κB和MMP-9阳性表达均下调,这说明早期应用抗变态反应药物孟鲁斯特不仅能够抑制抗原攻击引起的变应性炎症同时还能有效抑制鼻黏膜的组织重塑。
[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.
【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R765.21
本文编号：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.
【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R765.21
【引证文献】
相关硕士学位论文 前1条
1 汝海婧;鼻鼽散治疗常年性变应性鼻炎的临床疗效观察[D];黑龙江中医药大学;2011年
，本文编号：2481679
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