Use of dexmedetomidine in the preparation of a drug for protecting the structure of the lung tissue glycocalyx, preparation and use thereof

Abstract

This application relates to the use of dexmedetomidine in the preparation of a drug for protecting the glycocalyx structure of lung tissue, a formulation thereof, and its application, belonging to the field of lung injury technology. This application provides a formulation for protecting the glycocalyx structure of lung tissue, the formulation containing dexmedetomidine, which can protect the glycocalyx structure of lung tissue, thereby reducing lung injury and can be used to treat lung injury.

Description

Technical Field

[0001] This application relates to the field of lung injury technology, and more specifically, to the use of dexmedetomidine in the preparation of a drug for protecting the glycocalyx structure of lung tissue, its formulation, and its application. Background Technology

[0002] One-lung ventilation (OLV) is a respiratory management technique that utilizes a double-lumen bronchial tube or bronchial occluder to isolate the two lungs. It is widely used in video-assisted thoracoscopic surgery, minimally invasive cardiac surgery, esophageal surgery, and some vascular surgeries. However, OLV also carries significant pathophysiological risks, including ventilation / perfusion imbalance, hypoxemia, atelectasis, perfusion injury, re-expansion pulmonary edema, inflammation, and oxidative stress. Severe cases can lead to acute lung injury or even acute respiratory distress syndrome, which is one of the leading causes of postoperative death in thoracic surgery patients.

[0003] The respiratory system of infants and young children exhibits distinct anatomical and physiological characteristics: low functional residual capacity, limited oxygen reserve, high chest wall compliance but relatively low lung compliance, and a more horizontal diaphragm position. This significantly reduces their tolerance to hypoxia and high airway pressure, significantly increasing the risk of hypoxemia, atelectasis, pulmonary edema, and acute lung injury during one-lung ventilation. Summary of the Invention

[0004] This application provides the use of dexmedetomidine in the preparation of a drug that protects the glycocalyx structure of lung tissue, a formulation thereof, and its application. Dexmedetomidine can protect the glycocalyx structure of lung tissue, thereby reducing lung injury and can be used to treat lung injury.

[0005] This application is implemented as follows: In one aspect, this application provides a formulation for protecting the glycocalyx structure of lung tissue, the formulation containing dexmedetomidine.

[0006] Secondly, this application provides the use of the formulation of the first aspect in the preparation of a medicament for treating lung injury.

[0007] Thirdly, this application provides the use of dexmedetomidine in the preparation of a drug that protects the glycocalyx structure of lung tissue.

[0008] The beneficial effects of this application are at least as follows: In this application, dexmedetomidine can protect the glycocalyx structure of lung tissue by inhibiting the degradation and shedding of SDC-1 core protein and HS glycosaminoglycan side chains in lung tissue, as well as inhibiting the expression level of lung tissue glycocalyx-specific degradation enzyme HPSE, thereby reducing changes in glycocalyx structure during lung injury and thus alleviating lung injury. It can be used to treat lung injury. Attached Figure Description

[0009] To more clearly illustrate the technical solutions of the embodiments of this application, the accompanying drawings used in the embodiments will be briefly introduced below. It should be understood that the following drawings only show some embodiments of this application and should not be regarded as a limitation of the scope. For those skilled in the art, other related drawings can be obtained based on these drawings without creative effort.

[0010] Figure 1 Bar chart analysis of lung tissue W / D ratio; Figure 2 Images of HE staining of lung tissue from three groups of rats; Figure 3 A statistical graph of lung tissue damage scores based on HE staining. Figure 4 Transmission electron microscopy image of the ultrastructure of the glycocalyx of pulmonary capillary endothelium; Figure 5 Transmission electron microscopy image of the ultrastructure of the glycocalyx of the alveolar capillaries in the lungs; Figure 6 Immunofluorescence image of SDC-1 in lung tissue; Figure 7 Immunofluorescence images of the lung tissue in the HS group; Figure 8 Semi-quantitative analysis of the mean fluorescence intensity of SDC-1 in lung tissue; Figure 9 Semi-quantitative analysis of mean fluorescence intensity of HS in lung tissue; Figure 10 Images of HPSE immunohistochemical staining in lung tissue; Figure 11 Semi-quantitative analysis of the mean optical density value of HPSE in lung tissue; Figure 12 The results show the TNF-α levels in lung tissue homogenates as determined by ELISA. Figure 13 The results show the IL-6 levels in lung tissue homogenate as determined by ELISA. Figure 14 The protein expression band of SDC-1, a key component of the glycocalyx, in Western blotting. Figure 15 The protein expression band of HSPG, a key component of glycocalyx, in Western blotting. Figure 16 This is a statistical graph showing the relative expression levels of SDC-1 protein in Western blotting. Figure 17 This is a statistical graph showing the relative expression levels of HSPG protein in Western blotting. Figure 18The protein expression band of HPSE protein in Western blotting; Figure 19 This is a statistical graph showing the relative expression levels of HPSE protein in Western blotting. Figure 20 The protein expression band of p65 protein as determined by Western blotting. Figure 21 The protein expression band of p-p65 protein as determined by Western blotting. Figure 22 This is a statistical graph showing the relative expression levels of p65 protein in Western blotting. Figure 23 This is a statistical graph showing the relative expression levels of p-p65 protein in Western blotting. Figure 24 This is a graph showing the p-p65 / p65 ratio results in Western blotting. Detailed Implementation

[0011] The embodiments of this application will be described in detail below with reference to examples. However, those skilled in the art will understand that the following examples are for illustrative purposes only and should not be considered as limiting the scope of this application. Unless otherwise specified in the examples, conventional conditions or conditions recommended by the manufacturer shall apply. Reagents or instruments whose manufacturers are not specified are all commercially available conventional products.

[0012] The following detailed description, in conjunction with examples, illustrates the application, formulation, and application of dexmedetomidine in the preparation of a drug for protecting the glycocalyx structure of lung tissue.

[0013] Experimental methods: 1. Animal grouping and administration Eighteen SD rats were randomly divided into three groups: two-lung ventilation (TLV), one-lung ventilation (OLV), and dexmedetomidine (DEX). The TLV group underwent endotracheal intubation and received two-lung mechanical ventilation for 2 hours. Both the OLV and DEX groups established an OLV model, initially undergoing left-lung one-lung ventilation for 1.5 hours, followed by two-lung ventilation for 0.5 hours. In the DEX group, a loading dose of dexmedetomidine (5 μg / kg) was slowly injected via the femoral vein 15 minutes before the start of one-lung ventilation, followed by a continuous infusion at a rate of 2.5 μg / kg / h until the experimental endpoint. The TLV and OLV groups received the same volume of saline in the same manner. All rats (TLV, OLV, and DEX groups) received rocuronium bromide (0.6 mg / kg) via the femoral vein 5 minutes before the start of one-lung ventilation. Although the TLV group did not undergo one-lung ventilation, the timing of muscle relaxant administration was based on the time when one-lung ventilation began in the OLV group to ensure consistent treatment across all groups. The ventilator parameters were set as follows: During TLV, a tidal volume of 10 ml / kg, a respiratory rate of 80 breaths / min, an IRR of 1:1.5, and an inspiratory oxygen concentration of 100% were used; during OLV, the tidal volume decreased to 8 ml / kg, the respiratory rate increased to 100 breaths / min, the IRR remained at 1:1.5, and the inspiratory oxygen concentration remained at 100%.

[0014] All animal experimental procedures and feeding procedures in this study followed the National Institutes of Health's Guidelines for the Feeding and Use of Laboratory Animals and were approved by the Ethics Committee of the Children's Hospital Affiliated to Chongqing Medical University (Approval No.: CHCMU-IACUC20251105001).

[0015] The control group (TLV group) was treated with the following steps: After weighing the rats, they were anesthetized by intraperitoneal injection of 2% sodium pentobarbital solution at a dose of 50 mg / kg. After successful anesthesia, endotracheal intubation was performed using a 20G indwelling cannula. The rats were then fixed in a supine position on a heated pad with their left hind limb abducted and immobilized to fully expose the groin area. The femoral vein was carefully dissected to approximately 0.8–1.0 cm using a glass needle, and a 5-0 silk suture was passed through both the proximal and distal ends of the vein for later use. The distal end of the femoral vein was pre-ligated, and the proximal suture was lifted to block blood flow. A "V"-shaped incision was made on the vein wall between the ligation suture and the proximal traction suture using microscissors, with the incision diameter approximately one-third of the vessel circumference. A 24GY closed intravenous catheter, pre-filled with heparinized saline (20 U / mL), was slowly inserted proximally to the heart about 1.0–1.5 cm through the incision. After confirming clear flow of dark red blood, the catheter and blood vessel were ligated together with a silk suture at the proximal end, and then further secured with a silk suture at the distal end. Once the catheter was confirmed to be patent and without bleeding, the incision was covered with saline-moistened gauze, and a micro-infusion pump was connected to the catheter tip for later use. Throughout the procedure, the rat was placed on a constant-temperature heating pad (37°C) to maintain its body temperature, and vital signs such as respiration, heart rate, pulse oximetry, blood oxygen saturation, and mucosal color were closely monitored.

[0016] The specific steps for establishing the OLV model (left main bronchus intubation) are as follows: After anesthesia, endotracheal intubation, and mechanical ventilation, followed by femoral vein puncture and cannulation in rats, and confirmation of stable condition, correct cannulation placement, and symmetrical lung expansion, the cannula was advanced into the left main bronchus using the deep intubation method to establish a left-lung one-lung ventilation model. A 20%–30% increase in peak airway pressure compared to two-lung ventilation, and a left-sided chest rise and fall with the ventilator rhythm while the right-sided chest remained unchanged, preliminarily indicated successful left main bronchus intubation. For further confirmation, the ventilator tubing was briefly disconnected and reconnected, and end-expiratory carbon dioxide waveform and pressure changes were observed. After confirming successful intubation, ventilator parameters were adjusted, and one-lung ventilation was initiated. After 1.5 hours of one-lung ventilation, the cannula was withdrawn into the main trachea (restoring a depth of approximately 2.0 cm) to allow the right lung to re-expand, and two-lung ventilation was continued for another 0.5 hours. This method, verified through repeated open-chest experiments, confirms its feasibility and accurate positioning, demonstrating its advantages of being non-invasive and simple to perform.

[0017] 2. Specimen Collection After the rat experiments, rats were euthanized by exsanguination of the abdominal aorta under deep anesthesia. The abdominal cavity was opened, the abdominal aorta was exposed, and after confirming death by cutting the aorta, the thorax was immediately opened. The diaphragm was cut upwards along the midline of the abdomen, and then the thoracic cavity was incised along the anterior midline of the sternum to fully expose the heart and lung tissues. The pericardium was opened with ophthalmic scissors, and the heart and hilar vessels were freed. Under clear direct vision, the connective tissue around the hilum was gently separated with blunt forceps, and the right lung (including the upper, middle, lower, and accessory lobes) was removed whole along the right main bronchus. The right lung was placed in pre-cooled sterile saline (4°C) and quickly rinsed 1-2 times (approximately 10 seconds each time), with gentle agitation to remove residual blood from the tissue surface. The surface moisture was then absorbed with sterile filter paper. Throughout the entire procedure, traction and compression of the lung tissue were avoided to ensure no mechanical damage to the specimen.

[0018] Based on the experimental design, the lobes of the right lung were further divided into different areas for processing: (1) Right upper lobe: used for lung wet / dry weight ratio determination; (2) Right middle lobe of lung: Immediately place in 4% paraformaldehyde and fix at room temperature for 24-48 hours (fixation liquid volume is more than 10 times the tissue volume) for subsequent histopathological examination; (3) Right lower lobe: Placed on an ice plate in a pre-cooled sterile culture dish, the tissue was cut into small pieces of about 1-2 mm³ with a sterile scalpel blade, and the tissue pieces were aliquoted into pre-labeled cryovials with pre-cooled forceps, and then quickly frozen in liquid nitrogen. Afterward, the tissue was transferred to a -80°C freezer for subsequent molecular biological detection. (4) Right accessory lobe of lung: Place it on a pre-cooled sterile culture dish on an ice plate, cut the tissue into small pieces of 1mm × 1mm × 1mm with a sterile scalpel blade, and quickly immerse it in glutaraldehyde fixative containing lanthanum nitrate at 4℃ for 2-4 hours (the volume of fixative should be more than 20 times the volume of the tissue) for observation by transmission electron microscopy.

[0019] 3. Experimental Results and Analysis (1) Measurement of wet / dry weight ratio of lung tissue The upper lobe of the right lung of a rat was placed in pre-cooled sterile saline to wash away bloodstains. Surface moisture and residual blood were gently blotted dry with sterile filter paper. The lobe was then placed on pre-weighed aluminum foil, and its wet weight (W) was measured using a precision electronic balance, accurate to 0.1 mg. The tissue, along with the aluminum foil, was then placed in a 60°C oven for 48–72 hours until constant weight was achieved (the difference between two consecutive weighings was less than 0.2 mg). This value was recorded as the dry weight (D) of the lung tissue. The ratio of wet weight to dry weight (W / D ratio) was calculated as an indicator of lung tissue water content, reflecting the severity of pulmonary edema.

[0020] Reference Figure 1The lung tissue W / D ratio measurement results showed that the W / D ratio in the OLV group was significantly higher than that in the TLV group (P<0.0001), suggesting increased alveolar-capillary barrier permeability and pulmonary edema formation after one-lung ventilation. Compared with the OLV group, the W / D ratio in the DEX group was significantly lower (P<0.01), indicating that dexmedetomidine can protect alveolar-capillary barrier permeability and reduce pulmonary edema.

[0021] (2) HE staining was performed on the right middle lobe sample and the HE staining image was obtained. The magnification of the HE staining image was ×200 and the scale bar was 100μm.

[0022] Reference Figure 2 HE staining results showed that the lung tissue of rats in the TLV group had a clear and intact structure, with only a small number of bronchiolar epithelial cells sloughed off, rare granulocyte infiltration in the alveolar walls, and no significant widening of the alveolar septa. Compared with the TLV group, the OLV group showed obvious pathological damage in the lung tissue: some bronchiolar epithelial cells had loose and pale cytoplasm, eosinophilic material was visible in the bronchiolar and alveolar cavities, a large number of granulocytes were infiltrated in the alveolar walls, the alveolar walls were significantly thickened over a large area, the alveolar septa were significantly widened, and the alveolar cavities were narrowed or collapsed, suggesting that OLV successfully induced ALI in young rats. Compared with the OLV group, the pathological damage in the lung tissue of the DEX group was significantly reduced, the thickening of the alveolar walls and alveolar septa was alleviated, the inflammatory cell infiltration was reduced, and the alveolar structure was more intact.

[0023] (3) Assessment of lung injury severity Semi-quantitative scoring of lung tissue pathological sections was performed according to the acute lung injury scoring criteria recommended in the official symposium report of the American Thoracic Society. The scoring process was conducted by two pathologists who were not familiar with the grouping information, using a double-blind method, with each scoring independently, and the average of the two scores was taken as the final result.

[0024] The Lung Injury Score (LIS) is a semi-quantitative assessment based on the following five indicators: ① intraalveolar hemorrhage; ② alveolar congestion; ③ alveolar wall / alveolar membrane thickness; ④ alveolar neutrophil infiltration; and ⑤ interstitial neutrophil infiltration. Each indicator is scored according to the severity of the lesion: 0 (very mild injury), 1 (mild injury), 2 (moderate injury), 3 (severe injury), and 4 (very severe injury). The sum of the scores for each indicator is the Lung Injury Score (LIS).

[0025] Among them, the semi-quantitative lung injury scoring results are as follows: Figure 3 The results showed that LIS was significantly higher in the OLV group than in the TLV group (P<0.0001); and significantly lower in the DEX group compared to the OLV group (P<0.0001). These results indicate that dexmedetomidine can effectively improve lung tissue pathological damage caused by one-lung ventilation.

[0026] (4) The morphological changes of the glycocalyx layer of pulmonary vascular endothelial cells and alveolar epithelial cells were observed using lanthanum nitrate tracer electron microscopy cytochemistry technique.

[0027] Transmission electron microscopy results showed that a continuous, dense, and uniform flocculent glycocalyx layer was visible on the luminal surface of the lung capillary endothelial cells in the TLV group rats. The structure was intact, the boundaries were clear, and no obvious breakage or detachment was observed (Figure 4). Compared with the TLV group, the glycocalyx layer on the surface of the lung capillary endothelial cells in the OLV group rats was significantly thinner and sparser, and discontinuously distributed. In some areas, the glycocalyx was completely absent, and the endothelial cell membrane was exposed. Figure 4 Compared with the OLV group, the DEX group showed significant improvement in the glycocalyx layer of the pulmonary capillary endothelium, characterized by increased glycocalyx thickness, restored continuity, and a denser flocculent structure compared to the OLV group. Figure 4 ).

[0028] In addition, according to Figure 5 The results showed that the ultrastructural changes of the alveolar epithelial glycocalyx were consistent with those of the endothelial glycocalyx. In the TLV group, the alveolar epithelial cell luminal glycocalyx layer of rats was continuous, dense, and structurally intact; in the OLV group, the alveolar epithelial glycocalyx layer was significantly thinner and sparser, with loss of continuity and local glycocalyx detachment; in the DEX group, the alveolar epithelial glycocalyx layer thickness increased, the continuity was significantly improved, and the structure tended to be intact.

[0029] The above results demonstrate that one-lung ventilation not only disrupts the glycocalyx of pulmonary vascular endothelium but also leads to structural damage to the glycocalyx of alveolar epithelium. Dexmedetomidine can effectively protect the ultrastructural integrity of both the endothelium and epithelial glycocalyx. One-lung ventilation can induce alveolar-capillary barrier damage, and the glycocalyx, as a key barrier structure covering the luminal surface of pulmonary vascular endothelium and alveolar epithelial cells, can effectively reduce lung injury by protecting its structural integrity.

[0030] (5) Immunofluorescence staining to detect the expression levels of HS and SDC-1 in lung tissue HSPG, composed of the core protein SDC-1 and covalently linked HS side chains, serves as the main skeletal protein of the glycocalyx, providing structural support. HS, as the most abundant glycosaminoglycan side chain, is a core molecule maintaining the structural integrity and barrier function of the glycocalyx; the integrity of the HS side chain directly determines the functional status of the glycocalyx as the first line of defense in the alveolar-capillary barrier. SDC-1 is the most abundant transmembrane core protein expressed in lung tissue, and its extracellular domain is anchored to the cell surface via covalently bound HS side chains. The expression levels of these components collectively reflect the integrity of the glycocalyx structure.

[0031] Figure 6 and Figure 7Immunofluorescence staining results (using DAPI to counterstain cell nuclei) showed that HS and SDC-1 exhibited strong positive fluorescence signals in the lung tissue of rats in the TLV group, continuously distributed along the alveolar epithelium and vascular endothelium, with intact structures. Compared with the TLV group, the fluorescence signals of HS and SDC-1 in the OLV group were significantly weakened, and the continuity was lost, suggesting that OLV caused severe degradation of the glycocalyx core components. Compared with the OLV group, the fluorescence signals of HS and SDC-1 in the DEX group were significantly enhanced, and the continuity was improved. Semi-quantitative analysis results ( Figure 8 and Figure 9 The results showed that the average fluorescence intensity of HS and SDC-1 in the OLV group was significantly lower than that in the TLV group (P<0.0001); compared with the OLV group, the average fluorescence intensity of HS (P<0.0001) and SDC-1 (P<0.01) in the DEX group was significantly higher.

[0032] (6) Immunohistochemical (IHC) staining analysis of HPSE expression level in lung tissue Figure 10 Immunohistochemical staining results showed that HPSE in the lung tissue of TLV group rats was weakly positive, with very light staining. Compared with TLV group, HPSE positive staining was significantly enhanced in OLV group, with larger positive areas and deeper staining. Compared with OLV group, HPSE positive signals were sparsely distributed in DEX group, with smaller positive areas and lighter staining. Semi-quantitative analysis results ( Figure 11 The results showed that the AOD value of HPSE in the OLV group was significantly higher than that in the TLV group (P<0.0001); the AOD value of HPSE in the DEX group was significantly lower than that in the OLV group (P<0.001).

[0033] (7) Enzyme-linked immunosorbent assay (ELISA) to measure the levels of inflammatory factors TNF-α and IL-6 in lung tissue. ELISA results ( Figure 12 and Figure 13 The results showed that, compared with the TLV group, the levels of TNF-α and IL-6 in the lung tissue of the OLV group were significantly increased (P<0.0001); compared with the OLV group, the levels of TNF-α (P<0.05) and IL-6 (P<0.01) in the DEX group were significantly decreased.

[0034] (8) Western blot (WB) was used to detect the expression levels of SDC-1, HSPG, HPSE, NF-κB p65, and p-NF-κBp65 in lung tissue. Reference Figures 14-17Immunoblotting results further validated the changes in glycocalyx components. Compared with the TLV group, the expression levels of SDC-1 (P<0.0001) and HSPG (P<0.001) proteins were significantly decreased in the OLV group; compared with the OLV group, the expression levels of SDC-1 (P<0.001) and HSPG (P<0.05) proteins were significantly increased in the DEX group. There was no significant difference in the expression level of the internal reference protein β-Actin among the groups. Data are expressed as mean ± standard deviation. *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001, no significant difference in ns. Figures 14-17 The results further confirmed that one-lung ventilation can induce the degradation and shedding of key components of glycocalyx, HS and SDC-1, in lung tissue, while dexmedetomidine can significantly reduce the degradation and shedding of key components of glycocalyx, HS and SDC-1.

[0035] Reference Figures 18-19 Immunohistochemical staining showed that HPSE protein expression was significantly increased in the OLV group compared to the TLV group (P<0.0001), while HPSE expression was significantly decreased in lung tissue after dexmedetomidine intervention (P<0.0001); β-Actin expression levels remained consistent across groups. Combined with immunohistochemical analysis, it was found that one-lung ventilation induces upregulation of HPSE expression in lung tissue, and dexmedetomidine effectively antagonizes this effect, suggesting that dexmedetomidine may protect the integrity of the glycocalyx structure by inhibiting HPSE-mediated HS side chain cleavage. Data are expressed as mean ± standard deviation. *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001, no significant difference in ns.

[0036] Reference Figures 20-24 Immunoblotting results showed that the total p65 protein expression levels were comparable among the groups. The p-p65 / p65 ratio in the OLV group was significantly higher than that in the TLV group (P<0.0001), while the ratio in the DEX group was significantly lower than that in the OLV group (P<0.01). Here, p65 represents the NF-κB p65 protein expression level, and p-p65 represents the p-NF-κB p65 expression level. Data are expressed as mean ± standard deviation. *P<0.05,**P<0.01,***P<0.001,****P<0.0001, no significant difference in ns.

[0037] The results of immunohistochemical analysis showed that under one-lung ventilation, the NF-κB signaling pathway in lung tissue was significantly activated, which in turn promoted the release of large amounts of inflammatory factors TNF-α and IL-6; while after administration of dexmedetomidine, the activation state of this pathway and the expression of downstream inflammatory factors were effectively inhibited.

[0038] During one-lung ventilation, ischemia-reperfusion in the non-ventilated lung can trigger an inflammatory cascade centered on NF-κB. There is a mutually amplifying relationship between glycocalyx degradation and the inflammatory response: on the one hand, degradation products resulting from glycocalyx structural damage can participate in endogenous DAMPs and pattern recognition receptors such as Toll-like receptor 4 (TLR4), exacerbating NF-κB activation; on the other hand, NF-κB-driven transcription of inflammatory factors such as TNF-α can feedback-enhance HPSE expression, driving continuous glycocalyx degradation, thus forming an "inflammation-barrier disruption-inflammation" loop.

[0039] In summary, in this application, dexmedetomidine can protect the glycocalyx structure of lung tissue by inhibiting the degradation and shedding of SDC-1 core protein and HS glycosaminoglycan side chains in lung tissue, as well as inhibiting the expression level of lung tissue glycocalyx-specific degradation enzyme HPSE, thereby reducing changes in glycocalyx structure during lung injury and thus alleviating lung injury. It can be used to treat lung injury.

[0040] The above description is merely a specific embodiment of this application and is not intended to limit this application. Various modifications and variations can be made to this application by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of this application should be included within the protection scope of this application.

Claims

1. A formulation for protecting the glycocalyx structure of lung tissue, characterized in that, The formulation contains dexmedetomidine.

2. The formulation for protecting the glycocalyx structure of lung tissue according to claim 1, characterized in that, The formulation also contains a pharmaceutically acceptable carrier.

3. The formulation for protecting the glycocalyx structure of lung tissue according to claim 1 or 2, characterized in that, The formulation includes liquid, tablet, powder or capsule.

4. The use of the formulation according to any one of claims 1 to 3 in the preparation of a medicament for treating lung injury, characterized in that, Dexmedetomidine is used to protect the glycocalyx structure in lung tissue.

5. The application according to claim 4, characterized in that, The glycocalyx structure includes the endothelial glycocalyx structure of the pulmonary blood vessels and the epithelial glycocalyx structure of the alveoli.

6. The application according to claim 4, characterized in that, The dexmedetomidine is used to reduce the degradation and shedding of SDC-1 core protein and HS glycosaminoglycan side chains in lung tissue.

7. The application according to claim 4, wherein the lung injury includes one-lung ventilation lung injury.

8. Application of dexmedetomidine in the preparation of drugs that protect the glycocalyx structure of lung tissue.

9. The application according to claim 8, characterized in that, Dexmedetomidine is used to inhibit the expression level of HPSE, a glycocalyx-specific degradative enzyme in lung tissue.

10. The application according to claim 8, characterized in that, The dexmedetomidine is used to inhibit the degradation and shedding of SDC-1 core protein and HS glycosaminoglycan side chains in lung tissue.

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