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The Roles and Mechanism of the Expression of MMP-9 and TNF-α in the Pathogenesis of Upper and Lower Respiratory Inflammation

Author: LiuWenJun
Tutor: ZuoGang
School: Luzhou Medical College
Course: Otorhinolaryngology
Keywords: Allergic Rhinitis Asthma Matrix metalloproteinase-9 Tumor necrosis factor -α Eosinophils Mast cells Rats
CLC: R364.5
Type: Master's thesis
Year: 2010
Downloads: 92
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Abstract


Objective: To build allergic rhinitis and allergic asthma animal model, respectively, to detect the nasal mucosa and lung tissue eosinophils, mast cells, matrix metalloproteinase-9 and tumor necrosis factor-α expression of matrix metalloproteinase-9 and tumor necrosis factor-α consistency in the role and mechanism of the upper and lower respiratory tract inflammation reaction, which provide a theoretical basis for the treatment of inflammatory diseases of the upper and lower respiratory tract. Methods: 6-8 weeks male SD rats (body weight 160 ~ 200g) 40 Zhi, were randomly divided into four groups: the allergic rhinitis group of 10 allergic rhinitis control group of 10 allergic asthma group 10 allergic asthma in the control group 10. Allergic rhinitis group to give 20mg of ovalbumin was dissolved in 1 ml of physiological saline, to 30mg of aluminum hydroxide immunoadjuvant intraperitoneal injections, for eight consecutive times (every other day), starting from 16 days to 5% ovalbumin physiological saline solution intranasal, 50μl / side, continuous 10d. Allergic rhinitis control group of 10 rats, 1ml saline plus 30mg aluminum hydroxide intraperitoneal injection of saline intranasally, the same time with the allergic rhinitis group. Allergic asthma in rats 10, 1 day, 8 days, 15 days of intraperitoneal injection of 5% egg albumin 1ml; intraperitoneal injection of ovalbumin on day 16, with 1% ovalbumin atomized inhalation 30min daily 1 for 10 consecutive days. Allergic asthma control group of 10 rats by intraperitoneal injection and inhalation of saline instead of ovalbumin, the same law, the same amount over the same period. After each excitation of the experimental group and control group were observed for 30 minutes. Allergic rhinitis group and the control group were killed after the last challenge, 30min; allergic asthma group and the control group of rats were killed after 2h nebulized. 2% sodium pentobarbital (2ml/kg) intraperitoneal anesthesia to take nasal mucosa, complete remove lung tissue fixed quickly placed in 4% paraformaldehyde fixative. HE staining and toluidine blue staining were detected model of allergic rhinitis and allergic asthma in the nasal mucosa and lung tissue eosinophils, mast cells express immunohistochemical SP method detects the matrix metalloproteinase the organization - 9 and tumor necrosis factor-α expression, statistical analysis of the relationship between the expression of these indicators and the upper and lower respiratory tract inflammation response consistency. Results: allergic rhinitis, allergic asthma rats ovalbumin excitation appeared typical of allergic rhinitis, asthma symptoms, and these symptoms gradually reduce after 2h (score gt; 5 points). The control group only mild sneezing, scratching nose movements and breathing speed up the symptoms. Allergic rhinitis, allergic asthma group nasal cilia lodging, shedding gland hyperplasia, edema, expansion the lamina propria move, veins and capillaries in varying degrees, the mucosal epithelial lower visible eosinophils and mast cell infiltration; lung tissue biopsy shown bronchial epithelial hyperplasia, mucus gland secretion, bronchospasm, contraction, peribronchial eosinophil infiltration of lymphocytes. Allergic rhinitis, nasal and lung tissue of allergic asthma in the control group no significant eosinophil infiltration, only small blood vessels around the scattered distribution of mast cells; allergic rhinitis and allergic asthma the model nasal mucosa and lung tissue eosinophils, mast cells, and matrix metalloproteinase-9 and tumor necrosis factor-α-positive cell count was significantly greater than the corresponding control group (all P lt; 0.05). Allergic rhinitis, allergic asthma group nasal mucosa and lung tissue matrix metalloproteinase-9 and tumor necrosis factor-α expression, the expression of matrix metalloproteinase-9 and the number of eosinophils, matrix metalloproteinase-9 expression and the number of mast cells, the expression of tumor necrosis factor-α, and the number of eosinophils, tumor necrosis factor-α expression and mast cell numbers were positively correlated (all P lt; 0.05), and matrix metalloproteinase-9 and tumor necrosis factor-α expression, respectively, consistent with the nasal mucosa and lung tissue of the experimental group. Conclusion: (1) ovalbumin SD rats were able to successfully establish allergic rhinitis and allergic asthma in animal models, and from the perspective of histopathological prove allergen repeated excitation / lower respiratory tract can also cause / The respiratory inflammatory changes consistent, that is, the upper and lower respiratory tract inflammation reaction. (2) infiltration of eosinophils and mast cells, as well as matrix metalloproteinase-9 and tumor necrosis factor-α are involved in the pathophysiology of allergic rhinitis and asthma. (3) The matrix metalloproteinase-9 and tumor necrosis factor-α may play an important role in the upper and lower respiratory tract inflammation response consistency; tumor necrosis factor-α precursor and its mechanism may be related to the degradation of matrix metalloproteinase-9, making it the active form , and tumor necrosis factor-α can be induced by a variety of cells in the expression of matrix metalloproteinase-9, thus degrading the basement membrane and extracellular matrix components involved in the infiltration of eosinophils and mast cells. (4) The experimental results prove that the upper and lower respiratory tract inflammatory response consistency in clinical work should pay attention to the close ties of both allergic rhinitis and allergic asthma, bronchial asthma should pay attention to the treatment of allergic rhinitis / bronchial asthma / allergic rhinitis assessment, in order to improve the efficacy of allergic rhinitis and bronchial asthma.

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