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Effect of Ginkgo Biloba Extract on Expression of Matrix Metalloproteinase-9 in Chronic Asthmatic Mice and Its Mechanism

Author: LiYan
Tutor: QiHaoWen
School: Fourth Military Medical University
Course: Internal Medicine
Keywords: Ginkgo biloba extract Asthma Airway remodeling Matrix metalloproteinase-9 Platelet-activating factor NF-κB
CLC: R285.5
Type: Master's thesis
Year: 2008
Downloads: 86
Quote: 2
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Abstract

Airway remodeling (Remodeling) also known as airway remodeling or airway remodeling, chronic asthma, recurrent pathophysiological basis, it is closely related with asthma impairment of lung function and airway hyperresponsiveness. Degradation and deposition of extracellular matrix (Extracellular matrix, ECM) imbalance is an important reason to cause structural abnormalities of the airway wall, destruction of the lung parenchyma and stromal hyperplasia, ECM degradation by matrix metalloproteinases (Matrix metalloproteinase, MMPs), including matrix metalloproteinase -9 (Matrix metalloproteinase 9, MMP-9) is a zinc-dependent proteases, matrix metalloproteinase-9 catalytic Group area containing three repeat class II binding domain of fibronectin, determine its gelatin and elastin fibers The substrate specificity, the main degradation IV type V collagen type. Recent studies have shown that MMP-9 play an important role in airway inflammation and tissue remodeling in patients with bronchial asthma. Nuclear factor-κB (nuclear factor kappa B, NF-κB) is a multi-purpose nuclear transcription factor, with a wide range of biological activity, not only involved in the inflammatory response of asthma, is also involved in the asthmatic airway remodeling process. The study shows that the platelet activating factor (Platelet-activating Factor, PAF) is the NF-κB-specific activating factor, PAF activate NF-κB through early to cause a variety of inflammatory reactions. Ginkgo biloba extract is a specific inhibitor of PAF. Studies have shown that MMP-9 is the target of the NF-κB factor, NF-κB increase may be a direct result of the expression of MMP-9 increased However, studies have shown that PAF whether to influence the expression of MMP-9 by affecting the NF-κB. Therefore, this study is divided into two parts, to explore the Ginkgo biloba extract on chronic asthmatic mice expressing the impact of MMP-9 and Ginkgo biloba extract affected the expression of MMP-9 by inhibiting the expression of NF-κB. Part I: Objective: To explore the Ginkgo biloba extract on the expression of MMP-9 in chronic asthmatic mice. Methods: asthma mouse model of airway remodeling, 40 BALB / c mice were divided into 4 groups: control group, asthma group, the ginkgo leaf intervention group, dexamethasone group random number. Chicken egg albumin (ovalbumin, OVA)-sensitized and to stimulate preparation mice model of chronic asthma. Of lung tissue stained by hematoxylin - eosin staining airway remodeling. Immunohistochemical mice lung tissue measured the expression of MMP-9. RT-PCR analysis of MMP-9 mRNA expression in mouse lung tissue. Results: Asthma animals appear to wall thickening, smooth muscle hyperplasia, increased mucus secretion, airway remodeling characteristic changes of immunohistochemical staining shows the layers of the airway cells and inflammatory cells are the expression of MMP-9 increased and MMP-9 mRNA levels were also significantly higher. Dexamethasone group and Ginkgo biloba intervention group compared with the asthma group was mild inflammation, smooth muscle hyperplasia, mucus secretion is not obvious, immunohistochemical staining showed each cell MMP-9 expression also decreased the level of MMP-9 mRNA expression decreased. The difference was statistically significant compared with the control group. Conclusion: The long-term inhalation of allergens can lead to airway remodeling, MMP-9 plays a role in airway remodeling, the intervention effect of Ginkgo biloba there may be some connection between the PAF and MMP-9. Part II: Objective: To explore the Ginkgo biloba extract on chronic asthmatic mice expression of NF-κB and its relationship with the expression of MMP-9: the establishment of a murine asthma model of airway remodeling, 40 BALB / c mice random number is divided into 4 groups: control group, asthma group, the ginkgo leaf intervention group, dexamethasone group. OVA-sensitized and to stimulate preparation mice model of chronic asthma. Of lung tissue stained by hematoxylin - eosin staining airway remodeling. Immunohistochemical mice lung tissue measured the expression of NF-κB. RT-PCR analysis of each group of mice lung tissue NF-κB mRNA expression. For NF-κB activation analysis of the correlation between the expression of MMP-9. Results: Asthma animals appear to wall thickening, smooth muscle hyperplasia, increased mucus secretion, airway remodeling characteristic changes, immunohistochemical staining showed that NF-κB was activated, and NF-κB mRNA levels were also significantly higher. Dexamethasone intervention group and Ginkgo biloba intervention group compared with the asthma group was mild inflammation, smooth muscle hyperplasia, mucus secretion is not obvious, immunohistochemical staining showed decreased NF-κB activation of NF-κB mRNA expression level to reduce the control group, the difference was statistically significant. And NF-κB activation and MMP-9 expression was positively correlated. Conclusion: Ginkgo biloba extract may cause reduced chronic asthmatic mice NF-κB activation, reduction of NF-κB activation may lead to further reduction of the expression of MMP-9.

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