Abstract: Chronic Obstructive Pulmonary Disease (COPD) is a common chronic respiratory disease characterized by persistent airflow limitation. The pathological mechanism is not fully elucidated, but studies have shown that it is associated with multiple inflammatory cells and inflammatory mediators, and COPD airway remodeling is largely due to the imbalance of proteases and anti-proteases. In this paper, we describe the relationship between MMP-9/TIMP-1 and COPD airway remodeling, and suggest that MMP-9/TIMP-1 imbalance is closely related to the development of COPD. Using MMP-9 and TIMP-1 as the action targets to regulate the balance of MMP-9/TIMP-1, we provide new ideas and avenues for the development of new drugs for the clinical treatment of COPD and airway remodeling repair in COPD. Keywords: MMP-9; TIMP-1; COPD; airway remodeling COPD is a common chronic respiratory disease characterized by persistent airflow limitation. COPD symptoms are characterized by chronic inflammation of the airways, pulmonary vasculature, and lung parenchyma, resulting in the repair of repeated airway wall damage and eventually airway remodeling. Inflammatory cells and inflammatory mediators trigger chronic inflammation, and airway remodeling is largely caused by protease and anti-protease imbalance. Among them, MMP-9 and TIMP-1 are the current research hotspots. Therefore, this paper will explore the pathological mechanism of COPD airway remodeling from the imbalance of MMP-9/TIMP-1, and provide new ideas and approaches for the clinical treatment of COPD and the development of new drugs for COPD airway remodeling repair. 1.Protease/anti-protease imbalance The dynamic balance of protease/anti-protease is the main factor to ensure the normal structure of lung tissue from damage. The detailed mechanism of alveolar wall destruction is not fully understood, but the solubilizing activity of proteases exceeds the inhibiting activity of anti-proteases is one of the main reasons. An increase in protease or a deficiency or relative decrease in antiprotease may cause a disproportionate ratio of protease to antiprotease, thereby damaging the lung tissue. Studies have shown that MMP can cause severe damage to the ECM. 2, MMP-9 MMP is a family of proteases structurally dependent on zinc and calcium ions, and it has a strong degradation effect on ECM. mMP can also hydrolyze other mediator activities and some of these membrane-bound processes will indirectly regulate the inflammatory process. Twenty-six members of the MMP family have been isolated and identified, and they are classified as classic and novel according to their structural characteristics and their sensitivity to acting substrates. The classic type includes interstitial collagenase, gelatinase, interstitial lysozyme, and elastase, while the novel type includes secretory MMP, membrane MMP, and other MMPs whose roles are still unclear, of which gelatinase B (MMP-9) and gelatinase A (MMP-2) are the main enzymes involved in airway remodeling in chronic bronchitis, asthma, and COPD. Gelatinases mainly degrade some basement membrane substances and have important effects on cellular immunity, tumor metastasis, tissue inflammation, fibrosis and other action links. Among them, MMP-9 has the largest molecular weight, and its normal genetic characteristics show that it can maintain and regulate normal tissue function. mmp-9 is present in many cells, like tumor cells, macrophages, neutrophils, fibroblasts, etc. MMP-9 degrades the ECM and basement membrane of airways and lungs, participates in their remodeling and inflammatory cell chemotaxis, and plays an important role in the pathogenesis of COPD. One study found that MMP-9 was found to be elevated in BALF and airway biopsy tissues of COPD patients. 3, MMP-9 and TIMP-1 TIMP is a natural MMP inhibitor. In general, ECM degradation and synthesis are in balance with each other, and the stability of the internal environment of the ECM depends on the balance between MMP and TIMP. TIMP usually binds MMP in a 1:1 molar ratio to form MMP-TIMP compounds, thus preventing MMP fusion substrates, inhibiting MMP activity and forming an endogenous system for regulating MMP in vivo. there are five subclasses of TIMP TIMP-1 is the most active and specifically inhibits the activity of MMP-9. TIMP also acts as a cell growth factor, precipitating ECM and weakening the ECM degradation response, an important manifestation of airway fibrosis, indicating that airway remodeling has occurred. TIMP-l is also thought to act as a transcriptional repressor to inhibit MMP gene transcription, as TIMP- The amount of TIMP is smaller than the amount of MMP, resulting in a decrease in the inhibitory effect of TIMP on MMP, and MMP becomes more active, resulting in an accelerated degradation response of ECM. 4, the relationship between MMP-9/TIMP-1 and COPD airway remodeling airway remodeling will make the inner wall of the airway thicken, narrowing the tracheal space, increasing the internal resistance of the airway, impeding normal breathing, and even triggering COPD. the reason for airway remodeling, an important reason is the imbalance between ECM precipitation and degradation, and MMP-9 has an important impact on ECM precipitation and degradation. COPD inflammation is mainly caused by some inflammatory cells, especially macrophages, which have the most obvious effect. Under the action of MMP-9, alveolar macrophages will produce can be stimulated by lipopolysaccharide and IL-1β, etc., resulting in over-expression of MMP-9, which directly affects ECM degradation, tissue remodeling and inflammatory response. A study of MMP-9 and TIMP-1 levels in the serum of patients with COPD revealed that MMP-9 and TIMP-1 levels in the serum of patients with COPD were significantly higher than in healthy subjects, while MMP-9/TIMP-1 was lower than in normal subjects, and the ratio was positively correlated with FEV1. A positive correlation was found between MMP-9, TIMP-1 and IL-8 in the serum of COPD patients, while a negative correlation was found with IL-2. And there was a negative correlation with IL-2, indicating that when inflammation deepened, the amount of MMP-9 increased and the amount of TIMP-1 decreased, the more severely the lung tissue was damaged by MMP-9, and the remodeling effect of TIMP-1 on the damaged airways was weakened. The concentration of serum MMP-9 was significantly increased in patients with acute exacerbation of COPD, and the concentrations of MMP-9, TIMP-1 and MMP-9/TIMP-1 ratio were negatively correlated with the degree of airway obstruction; when there was more MMP-9 than TIMP-1, it indicated that inflammation occurred in the airway wall, and when there was less MMP-9 than TIMP-1, it indicated that the airway wall began to repair. All these studies suggest that MMP-9/TIMP-1 imbalance is an important mechanism causing COPD. The imbalance of MMP-9/TIMP-l ratio causes disorder of ECM metabolism, excessive deposition of collagen in the airway wall to thicken it, smooth muscle hyperplasia, leading to luminal narrowing and fibrosis, and finally causing airflow obstruction not completely reversible typical COPD airway remodeling pathological basis. 5, the outlook MMP-9/TIMP-1 imbalance and the development of COPD airway remodeling is closely related. At present, a lot of results have been achieved in both Chinese and Western medicine in regulating the balance between the two, but the principle of MMP-9/TIMP-1 balance has not been mastered yet. For this reason, this paper proposes the hypothesis: 1. More MMP-9 than TIMP-1 and inflammation of the airway wall occurs. This may be due to an increase in MMP-9 or a decrease in TIMP-1, indicating that there is an inflammatory response in the airway wall that is not repaired, or an increase in TIMP-1 values that is less than the increase in MMP-9 values, indicating that the inflammatory response and repair of the airway wall are occurring simultaneously, but the inflammatory response is predominant. 2. MMP-9 is less than TIMP-1, and airway wall repair begins. It may be due to the decrease in MMP-9 value, TIMP-1 value unchanged or increased, indicating that the airway wall repair without inflammatory response; or MMP-9 value increase is less than the TIMP-1 increase, indicating that there is both tissue repair and inflammatory response, but has been the main repair. If the mechanism of MMP-9 and TIMP-1 balance and the relationship between the inflammatory response and repair of airway wall and MMP-9/TIMP-1 values can be investigated, the balance point can be adjusted to effectively interfere with the inflammatory response and promote the repair of airway wall. Through the in-depth study of MMP-9 and TIMP-1, we can better elucidate the pathogenesis of airway remodeling in COPD, and at the same time, we can regulate the MMP-9/TIMP-1 balance with MMP-9 and TIMP-1 as the targets of action for prevention. The detection of MMP-9 levels in the serum of COPD patients can help analyze the study of the pathogenesis of patients, and the search for the ideal regulatory drug of MMP-9 is crucial for the prevention and treatment of COPD.