Effect Of Ginkgo Biloba Extract On Expression Of Matrix Metalloproteinase-9 In Chronic Asthmatic Mice And Its Mechanism

Airway remodeling is important pathological and physiological foundation in recurrent attacks of chronic asthma. It has correlation with injury of lung function and airway hyperreactivity (AHR). The imbalance of degradation and deposition in extracellular matrix (ECM), is one of important factors that causes structural abnormalities of airway wall, destruction of lung parenchyma and proliferative interstitium. ECM mainly was degraded by Matrix metalloproteinase (MMPs), and Matrix metalloproteinase 9 (MMP-9) is zinc-binding proteinase. It contain fibronectin type II–like repeats within their catalytic domain, resulting in a higher binding affinity to gelatin and elastin, and it mainly degrades type IV and V collagen. Recently ,studies indicate that MMP-9 has important function in airway inflammation and tissue remodeling in asthmatic patients. Nuclear factor kappa B (NF-κB) is an important transcription factor necessary for initiating and sustaining inflammatory and immune reactions. It also plays a role in asthmatic airway remodeling. It is well known that PAF is an characteristic inducer of NF-κB activation. PAF acts as a triggering molecule in initiating a variety of early inflammatory reactions by activating early NF-κB. Ginkgo Biloba Extract is characteristic inhibitor of PAF. In addition, researches indicated that transcription of the MMP-9 gene depends on the transcription factors of NF-κB. But , presently PAF inducing matrix metalloproteinase-9 expression via a nuclear factor-kappa B dependent pathway is still not well defined. Therefore, in the present study we describe experiments aimed at the influence of Ginkgo Biloba Extract on expression of MMP-9 in chronic asthmatic mice and the influence of Ginkgo Biloba Extract on expression of NF-κB in chronic asthmatic mice and the connection of NF-κB and MMP-9.Part 1AIM: To investigate the influence of Ginkgo Biloba Extract on expression of MMP-9 in chronic asthmatic mice.METHODS: Forty BALB/c mice were randomly divided into four groups: control group, asthma group, gingko biloba extract treatment group, dexamethasone (DXM) treatment group. Mice were sensitized and challenged with ovalbumin to establish the asthmatic model. The paraffin embedded sections of lung tissue underwent HE staining and the lung pathological changes were observed. Transcriptional levels of MMP-9 mRNA extracted in lung tissues were assessed by RT-PCR. The expression of MMP-9 in lung tissues is detected by immunohistochemistry.RESULTS: After repeated allergen challenge, obvious infiltration of inflammatory cells and proliferation of goblet cells and smooth muscle were demonstrated in mouse bronchi. Expression levels of MMP-9 in the epithelial cells of bronchi were significantly higher in asthmatic animals than in control animals. Compared with asthmatic group, there was mild inflammation reaction, decreased in collagen deposition and expression of MMP-9 in gingko biloba extract treatment group and DXM treatment group, and they were not significantly higher than that in control animals.CONCLUSION: Repeated exposure of allergen induces airway inflammation and remodeling. MMP-9 plays an important role in airway remodeling. Gingko biloba extract intervention demonstrates that PAF might have some connection with MMP-9.Part 2AIM:To investigate the influence of Ginkgo Biloba Extract on expression of NF-κB in chronic asthmatic mice and the connection of NF-κB and MMP-9.METHODS: Forty BALB/c mice were randomly divided into four groups: control group, asthma group, gingko biloba extract treatment group, dexamethasone (DXM) treatment group. Mice were sensitized and challenged with ovalbumin to establish the asthmatic model. The paraffin embedded sections of lung tissue underwent HE staining and the lung pathological changes were observed. Transcriptional levels of NF-κB mRNA extracted in lung tissues were assessed by RT-PCR. The expression of NF-κB in lung tissues is detected by immunohistochemistry. In addition, the correlation of expression of MMP-9 and NF-κB activity is analyzed by statistics.RESULTS: After repeated allergen challenge, obvious infiltration of inflammatory cells and proliferation of goblet cells and smooth muscle were demonstrated in mouse bronchi. Expression levels of NF-κB in the epithelial cells of bronchi were significantly higher in asthmatic animals than in control animals. Compared with asthmatic group, there was mild inflammation reaction, decreased in collagen deposition and expression of NF-κB in gingko biloba extract treatment group and DXM treatment group, and they were not significantly higher than that in control animals.And, there was obviously positive correlation between MMP-9 and NF-κB expression in asthma.CONCLUSION: Ginkgo Biloba Extract might cause decrease of NF-κB activity , and decrease of NF-κB activity might cause decrease of expression of MMP-9.