Use of a pharmaceutical composition in the preparation of a medicament for preventing and / or treating high altitude low pressure and low oxygen related diseases

Abstract

The application provides a kind of drug composition in preparation prevention and / or treatment of high altitude low pressure hypoxia related disease in the application of drug, belong to medical technology field.The drug is compound Manshanbai syrup, which is composed of Manshanbai, Rhamnus utilis, tumorous wind and menthol.The application discloses that the drug can improve the high altitude low pressure hypoxia related disease under low pressure hypoxia environment, reduce lung tissue inflammatory response, reduce vascular permeability and regulate oxygenation function, thereby effectively preventing and / or treating high altitude low pressure hypoxia related disease.The drug can significantly improve lung water content, blood gas index, inflammatory factor level and lung tissue pathological damage, and provide a safe and effective new treatment for high altitude pulmonary edema.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology, specifically relating to the use of a pharmaceutical composition in the preparation of a drug for the prevention and / or treatment of diseases related to high altitude, low pressure, and hypoxia. Background Technology

[0002] High-altitude hypoxia-related diseases refer to a comprehensive pathological state caused by the combined effects of low air pressure and low oxygen partial pressure after the body enters a high-altitude environment or rapidly enters such an environment. These diseases mainly include high-altitude respiratory diseases, acute mountain sickness, chronic mountain sickness, and hypoxia-related tissue damage. The common characteristics of these diseases are insufficient oxygen supply and imbalance of the internal environment, with respiratory system involvement being particularly prominent, manifesting as impaired pulmonary ventilation / gas exchange, decreased blood oxygen saturation, and tissue hypoxia. Patients may experience symptoms such as headache, fatigue, shortness of breath, palpitations, and loss of appetite within hours to weeks after entering a high-altitude environment. In severe cases, it can progress to high-altitude pulmonary edema or chronic mountain sickness, and even lead to multiple organ dysfunction, becoming a significant public health problem affecting the health of personnel stationed at high altitudes for training, construction workers, and travelers.

[0003] Although the high-altitude, low-pressure, and hypoxic environment is a major trigger for these diseases, their pathogenesis is not caused by a single factor, but rather involves a complex pathological process involving the coordinated dysregulation of multiple systems and links. Current research indicates that hypoxia can induce enhanced ventilation response and pulmonary vasoconstriction, leading to increased pulmonary artery pressure and uneven blood flow distribution. Simultaneously, hypoxia can induce endothelial cell dysfunction and disrupt tight junction structures, resulting in increased vascular permeability, by activating signaling pathways such as hypoxia-inducible factor. Furthermore, elevated oxidative stress levels, increased release of inflammatory factors, and abnormal expression of aquaporins under hypoxic conditions can further exacerbate tissue edema and organ damage. These multiple pathological processes interact and amplify each other, ultimately leading to a range of clinical manifestations from mild altitude sickness to severe organ damage, making the prevention and treatment of these diseases highly complex.

[0004] Currently, prevention and treatment methods for diseases related to high-altitude hypoxia mainly include stepwise acclimatization ascent, oxygen support, and pharmacological intervention. Commonly used drugs, such as dexamethasone, acetazolamide, calcium channel blockers, and phosphodiesterase inhibitors, primarily work by improving ventilation, reducing pulmonary artery pressure, or alleviating inflammation, making it difficult to systematically regulate the multifactorial damage induced by hypoxia. Furthermore, some drugs pose certain side effects risks during long-term or preventative use. In addition, for individuals with long-term exposure to high-altitude environments or repeated high-altitude entries, existing interventions remain significantly insufficient in improving overall hypoxia tolerance and maintaining homeostasis. Therefore, developing a novel drug or treatment regimen that is highly safe, suitable for prevention and early intervention, and capable of comprehensively regulating hypoxia responses at multiple targets has significant clinical value.

[0005] Compound Manshan White Sugar Syrup is a compound preparation made from raw materials including Manshan White, Rhus chinensis, Rhus chinensis, and menthol. Its quality standards are included in the "National Drug Standards (Revised)". This preparation has the effects of clearing heat and detoxifying, relieving cough and expectoration, and reducing inflammation and asthma. It has long been used in the clinical treatment of respiratory diseases such as acute and chronic tracheitis and bronchitis, and has a good safety profile and rich clinical application experience. From the perspective of traditional Chinese medicine theory and modern pharmacological research, multiple active ingredients in this compound have the potential to regulate inflammatory responses, improve microcirculation, reduce tissue edema, and enhance the body's anti-hypoxia ability. However, as of now, there is a lack of systematic research and clear technical solutions regarding the preventive and therapeutic effects of Compound Manshan White Sugar Syrup on the body's oxygenation status, vascular barrier function, and hypoxia-related system damage under high-altitude, low-pressure, and low-oxygen environments.

[0006] Given that high-altitude hypoxia-related diseases involve multiple factors, multiple pathways, and rapid disease progression, there is an urgent need to explore a prevention and treatment strategy that can comprehensively regulate oxygenation, vascular permeability, inflammatory response, and water metabolism under hypoxic conditions. Summary of the Invention

[0007] The purpose of this invention is to provide the use of a pharmaceutical composition in the preparation of a medicament for the prevention and / or treatment of diseases related to high altitude, low pressure, and hypoxia.

[0008] The specific technical solution of the present invention is as follows: This invention provides the use of a pharmaceutical composition in the preparation of a medicament for the prevention and / or treatment of diseases related to high altitude, low pressure, and hypoxia. The pharmaceutical composition is made from the following raw materials: Rhus chinensis, Rhus chinensis, Rhizoma Scutellariae, and Menthol.

[0009] Furthermore, the pharmaceutical composition is made from the following raw materials in the indicated weight ratios: 800-1000 parts of Rhus chinensis, 500-700 parts of Rhus chinensis, 200-400 parts of Rhizoma Sinensis, and 0.05-0.2 parts of menthol.

[0010] Furthermore, the pharmaceutical composition is prepared from the following weight ratio: 900 parts of Rhus chinensis, 600 parts of Rhus chinensis, 300 parts of Rhizoma Scutellariae, and 0.1 parts of Menthol.

[0011] Furthermore, the drug is a syrup.

[0012] Furthermore, the drug is Compound Manshan White Sugar Syrup.

[0013] Furthermore, the drug can reduce lung tissue water content and total protein concentration in bronchoalveolar lavage fluid, and reduce pulmonary endothelial barrier permeability, thereby alleviating pulmonary edema induced by hypotension and hypoxia.

[0014] Furthermore, the drug can increase the partial pressure of oxygen and carbon dioxide in arterial blood, promote the restoration of blood pH, and reduce lactic acid levels, thereby improving oxygenation disorders and acid-base imbalances caused by low pressure and low oxygen.

[0015] Furthermore, the drug can increase arterial blood potassium levels. + and Ca 2+ It lowers the level of hematocrit and hemoglobin concentration, thereby improving electrolyte imbalance and blood concentration caused by low pressure and low oxygen.

[0016] Furthermore, the drug can reduce the levels of pro-inflammatory cytokines such as tumor necrosis factor-α, interleukin-1β, interleukin-6, and interleukin-17, as well as myeloperoxidase and vascular endothelial growth factor in bronchoalveolar lavage fluid and serum, and increase the level of the anti-inflammatory factor interleukin-10, thereby improving the inflammatory response induced by hypobaric hypoxia and the pro-inflammatory-anti-inflammatory imbalance.

[0017] Furthermore, the drug can reduce the expression of hypoxia-inducible factor-1α and aquaporin 1 protein.

[0018] Furthermore, the high-altitude low-pressure hypoxia-related diseases are models of high-altitude respiratory diseases, acute mountain sickness, chronic mountain sickness, and hypoxia induced by low pressure and hypoxia.

[0019] The present invention has achieved the following beneficial effects: This invention proposes for the first time a novel use of Compound Manshan White Sugar Syrup in the prevention and / or treatment of diseases related to high-altitude hypoxia and low pressure. Experimental results show that the drug can: (1) significantly reduce pulmonary edema, manifested by a decrease in lung water content and bronchoalveolar lavage fluid protein levels; (2) improve oxygenation function, manifested by improvements in arterial blood oxygen partial pressure, carbon dioxide partial pressure, pH, and lactate levels; (3) regulate inflammatory responses, reducing inflammatory factors such as tumor necrosis factor-α and interleukin-6; (4) regulate key pathways, inhibiting the expression of hypoxia-inducible factor-1α and aquaporin 1; and (5) improve vascular permeability, with in vitro experiments showing a reduction in endothelial permeability. More importantly, compared with dexamethasone, a commonly used anti-inflammatory drug in clinical practice, Compound Manshan White Sugar Syrup exhibits equivalent or even superior pharmacological activity in multiple core indicators (cell protection, barrier repair, oxygenation improvement, and inflammation suppression). As a traditional Chinese medicine compound preparation, it has higher safety, fewer side effects, and is more suitable for long-term preventive use in people living in special high-altitude environments.

[0020] Obviously, based on the above description of the present invention, and according to common technical knowledge and conventional methods in the field, various other modifications, substitutions or alterations can be made without departing from the basic technical concept of the present invention.

[0021] The following detailed embodiments further illustrate the above-described content of the present invention. However, this should not be construed as limiting the scope of the present invention to the following embodiments. All technologies implemented based on the above-described content of the present invention fall within the scope of the present invention. Attached Figure Description

[0022] Figure 1 This image shows the in vitro protective effect of Compound Manshan White Sugar Syrup against hypoxia-induced damage to human umbilical vein endothelial cells (HUVECs). (A) CCK-8 assay; (B) Reactive oxygen species (ROS) assay; (C) Statistical results of ROS; (D) FITC-glucan permeability assay. (n=3, mean ± SEM) * p <0.05, ** p <0.01, *** p <0.001 indicates a difference compared to the normal group; # p <0.05, ## p <0.01, ### p <0.001 indicates a comparison with the model group; all comparisons were performed using one-way ANOVA.

[0023] Figure 2 The diagram shows the effects of Compound Manshan White Sugar Syrup on a rat model of high-altitude hypobaric hypoxia-related diseases. (A) Experimental time axis; (B) Lung water content; (C) Total protein concentration in bronchoalveolar lavage fluid; (D) Lung weight coefficient; (E) Spleen weight coefficient; (F) Heart weight coefficient; (G) Liver weight coefficient; (H) Kidney weight coefficient; (I) Arterial blood oxygen partial pressure; (J) Arterial blood lactate content; (K) Arterial blood carbon dioxide partial pressure; (L) Arterial blood pH; (M) Arterial blood potassium. + Content; (N) arterial blood Ca 2+ Content; (O) arterial blood hematocrit; (P) arterial blood hemoglobin content. (n=6, mean ± SEM, * p <0.05, ** p <0.01, *** p <0.001 indicates a difference compared to the normal group; # p <0.05, ## p <0.01, ### p <0.001 indicates a comparison with the model group; all comparisons were performed using one-way ANOVA.

[0024] Figure 3 This image shows the protein expression and pathological changes in lung tissue of a rat model of high-altitude hypoxia-related diseases induced by Compound Manshan White Sugar Syrup. (A) Representative bands of hypoxia-inducible factor-1α, aquaporin 1, and β-actin detected by Western blot; (B) Relative protein quantification of hypoxia-inducible factor-1α; (C) Relative protein quantification of aquaporin 1; (n=3). (D) Representative images of H&E staining; (E) Lung tissue injury score; (F) Serum creatine kinase isoenzyme concentration; (G) Serum aspartate aminotransferase concentration; (H) Serum alanine aminotransferase concentration; (I) Serum creatinine concentration; (J) Serum total cholesterol concentration. (n=6, mean ± SEM, *** p <0.001 indicates a difference compared to the normal group; # p <0.05, ## p <0.01, ### p <0.001 indicates a comparison with the model group; all comparisons were performed using one-way ANOVA.

[0025] Figure 4This image shows the changes in inflammatory factor levels in a rat model of high-altitude hypoxia-related diseases induced by Compound Manshan White Sugar Syrup. (AG) Concentrations of interleukin-17, vascular endothelial growth factor, tumor necrosis factor-α, interleukin-1β, interleukin-6, interleukin-10, and myeloperoxidase in bronchoalveolar lavage fluid; (HN) Concentrations of interleukin-17, vascular endothelial growth factor, tumor necrosis factor-α, interleukin-1β, interleukin-6, interleukin-10, and myeloperoxidase in serum. (n=6, mean ± SEM, ** p <0.01, *** p <0.001 indicates a difference compared to the normal group; # p <0.05, ## p <0.01, ### p <0.001 indicates a comparison with the model group; all comparisons were performed using one-way ANOVA. Detailed Implementation

[0026] The raw materials and equipment used in this invention are all known products, obtained by purchasing commercially available products; the compound Manshan Bai syrup is provided by Shuixian Pharmaceutical (Jianou) Co., Ltd., and is made from the following raw materials in the following weight ratio: 900 parts Manshan Bai, 600 parts Rhus chinensis, 300 parts Rhizoma Sinensis, and 0.1 parts Menthol.

[0027] Example 1: In vitro cell experiment on the improvement of hypoxia-induced vascular endothelial dysfunction by compound Manshan white sugar syrup. Impaired vascular endothelial barrier function is a key factor in the development of respiratory diseases at high altitudes. Low-pressure, hypoxic environments can induce oxidative stress in vascular endothelial cells, leading to increased reactive oxygen species levels, decreased cell viability, and disruption of intercellular junctions, ultimately resulting in increased vascular permeability and pulmonary edema. Therefore, inhibiting endothelial cell oxidative stress and reducing permeability are crucial for preventing and treating high-altitude pulmonary edema. This study evaluated the effect of Compound Manshan White Sugar Syrup on improving hypoxia-induced vascular endothelial dysfunction by constructing a hypoxia-induced hypoxia injury model in HUVEC cells.

[0028] 1. Drug treatment The test drug was Compound Manshan White Sugar Syrup, provided by Narcissus Pharmaceutical (Jian'ou) Co., Ltd. Due to the high sugar content of the stock solution, to avoid contamination and ensure experimental stability, it was sterilized by filtration through a 0.22 μm filter membrane in a clean bench before being dispensed and stored at 4 ℃ for later use. During the experiment, it was diluted to final concentrations of 0.03%, 0.1%, 0.3%, and 1.0% (v / v) using complete endothelial cell culture medium.

[0029] 2. Cell Culture HUVEC cells were cultured in complete endothelial cell culture medium and placed in a 37 ℃, 5% CO2 incubator.

[0030] 3. Establishment of the hypoxia model and drug treatment Depending on the specific testing requirements, HUVEC cells in the logarithmic growth phase were seeded into 96-well plates, 6-well plates, or Transwell chambers. After the cells adhered to the walls, they were cultured in a hypoxic environment of 2% O2 to simulate the low-oxygen environment of high altitude.

[0031] The experimental groups were as follows: normoxic control group, hypoxia model group, hypoxia + compound Manshan white sugar syrup treatment group (0.03%, 0.1%, 0.3%, 1% v / v), and hypoxia + positive control dexamethasone group (10 μM).

[0032] 4. CCK-8 assay for cell viability HUVEC cells were seeded at an appropriate density in 96-well plates, with 100 μL of cell suspension added to each well. After 24 h of culture, hypoxia treatment and drug intervention were performed. After 24 h, 36 h, and 48 h of treatment, the culture medium was discarded, and 100 μL of complete culture medium and 10 μL of CCK-8 reagent were added to each well. After incubation at 37 ℃ for 1–2 h, the absorbance was measured at 450 nm.

[0033] The results are as follows Figure 1 As shown in Figure A, compared with the normoxic group, hypoxia treatment significantly reduced cell viability; while intervention with Compound Manshan White Sugar Syrup significantly improved cell viability in a dose-dependent manner. Specifically, the degree of cell viability recovery in the 1.0% Compound Manshan White Sugar Syrup treatment group was comparable to that in the 10 μM dexamethasone group, and the cell survival rates in the 0.3% and 1.0% dose groups were higher than those in the dexamethasone group, suggesting that Compound Manshan White Sugar Syrup has a concentration-dependent protective effect against hypoxia-induced cell damage, and its effect at higher concentrations is superior to the positive control dexamethasone.

[0034] 5. Reactive oxygen species detection Intracellular reactive oxygen species (ROS) levels were detected using the DCFH-DA probe. After treatment, cells were added to DCFH-DA working solution and incubated at 37 °C for 30 min, followed by flow cytometry analysis.

[0035] The results are as follows Figure 1 As shown in B and 1C, hypoxia significantly increased the level of reactive oxygen species (ROS) in cells, while Compound Manshan White Sugar Syrup significantly reduced the level of ROS, suggesting that Compound Manshan White Sugar Syrup can alleviate hypoxia-induced oxidative stress in vascular endothelial cells.

[0036] 6. FITC-dextran permeability test Endothelial cell permeability was assessed using the Transwell system. HUVEC cells were seeded in the upper chamber of a Transwell cell line, and after monolayer formation, they were subjected to hypoxia and drug treatment. After treatment, FITC-dextran solution was added to the upper chamber, and after incubation for a certain period, the fluorescence intensity in the lower chamber was measured.

[0037] The results are as follows Figure 1 As shown in Figure D, hypoxia treatment significantly increased endothelial permeability, while intervention with Compound Manshan White Sugar Syrup significantly reduced FITC-glucan permeability. Compared with the 10 μM dexamethasone positive control group, the 0.3% and 1.0% Compound Manshan White Sugar Syrup treatment groups showed stronger permeability inhibition, indicating that it has the potential to protect against hypoxia-induced endothelial barrier dysfunction compared to dexamethasone.

[0038] 7. Conclusion The above results indicate that Compound Manshan White Sugar Syrup can improve the cell viability of HUVECs under hypoxic conditions, reduce the accumulation of intracellular reactive oxygen species, and decrease the permeability of the HUVEC monolayer, thereby improving hypoxia-induced vascular endothelial dysfunction. These results provide in vitro experimental evidence for the use of Compound Manshan White Sugar Syrup in the prevention and treatment of hypoxia-related vascular endothelial injury at high altitudes.

[0039] Example 2: Protective effect of Compound Manshan White Sugar Syrup on acute injury induced by simulated high altitude, low pressure, and hypoxia in rats. High-altitude, low-pressure, and hypoxic environments can cause oxygenation disorders, pulmonary vasoconstriction, impaired endothelial barrier function, and activated inflammatory responses, leading to increased pulmonary fluid exudation and pulmonary edema. This study used a hypobaric chamber to simulate an altitude of 6000 m to establish an acute hypobaric-hypoxic injury model in rats, evaluating the protective effect of Compound Manshan White Sugar Syrup against lung injury, oxygenation disorders, and systemic inflammatory responses induced by hypobaric-hypoxic conditions. Figure 2 A).

[0040] 1. Drug treatment Compound Manshan White Sugar Syrup was provided by Narcissus Pharmaceutical (Jianou) Co., Ltd. The test drug was dispensed and stored at 4 ℃. It was thoroughly mixed before use, and the dosage volume was calculated based on the rat's body weight and the set dose.

[0041] 2. Animal model establishment and grouping SD rats were randomly divided into the following groups (n=6): normal control group, model group, positive control dexamethasone group (4 mg / kg / d), low-dose compound Manshan white sugar syrup group (MSB-L, 10 mL / kg / d), and high-dose compound Manshan white sugar syrup group (MSB-H, 20 mL / kg / d).

[0042] Rats in each group were administered the drug by gavage for 5 consecutive days, with the total daily dose divided into two equal doses. Subsequently, all groups except the control group were placed in a hypobaric and hypoxic chamber simulating an altitude of 6000 m for 48 h, while the normal control group was housed under normobaric and normoxic conditions. After the hypobaric and hypoxic exposure, arterial blood, serum, bronchoalveolar lavage fluid, and major organ tissues were collected for subsequent analysis.

[0043] 3. Lung water content and organ index detection After euthanizing the animal, lung tissue was collected and weighed to determine the wet and dry weight of the lungs. The lung water content was calculated as follows: Lung water content = (wet weight - dry weight) / wet weight × 100%. Simultaneously, the weight coefficients for the lungs, spleen, heart, liver, and kidneys were calculated as follows: Organ weight / body weight × 100%.

[0044] like Figure 2 As shown in Figure B, compared with the normal group, the lung water content in the model group was significantly increased, indicating that simulated low-pressure and low-oxygen exposure at an altitude of 6000 meters can cause significant lung tissue water retention. The lung water content in both the MSB-L and MSB-H groups was significantly reduced, with the MSB-H group showing a greater reduction than the positive control dexamethasone group. This supports the claim that Compound Manshan White Sugar Syrup can effectively alleviate low-pressure and low-oxygen-induced pulmonary edema, and that its effect exceeds that of dexamethasone at high doses.

[0045] like Figure 2 As shown in the DH diagram, compared with the normal group, the organ coefficients of the lung, spleen, heart, and kidneys were significantly increased in the model group, while the organ coefficient of the liver was significantly decreased. After intervention with Compound Manshan White Sugar Syrup, the organ coefficients of the lung, spleen, and heart were significantly reduced, but there was no significant effect on the organ coefficients of the liver and kidneys. The above results indicate that Compound Manshan White Sugar Syrup can improve the changes in the relative weight of the lung, spleen, and heart caused by hypobaric hypoxia, but its regulatory effect on the abnormal organ coefficients of the liver and kidneys is not significant.

[0046] 4. Protein detection in bronchoalveolar lavage fluid After the low-pressure, low-oxygen exposure, bronchoalveolar lavage fluid was collected, centrifuged to remove cells and precipitate, and the supernatant was used to determine the total protein concentration. Results are as follows: Figure 2As shown in Figure C, the total protein concentration in the bronchoalveolar lavage fluid of the model group was significantly increased. After intervention with Compound Manshan White Sugar Syrup, the total protein concentration in the bronchoalveolar lavage fluid was significantly reduced, and the protein level in the bronchoalveolar lavage fluid of the MSB-H group was reduced to a level close to that of the dexamethasone positive control group. This indicates that Compound Manshan White Sugar Syrup and dexamethasone have equivalent and potent protective effects in reducing lung barrier damage and protein exudation induced by low pressure and hypoxia.

[0047] 5. Arterial blood gas analysis Arterial blood was collected from rats after the low-pressure hypoxia exposure, and arterial oxygen partial pressure, arterial carbon dioxide partial pressure, pH, lactate, and potassium were measured using a blood gas analyzer. + Ca 2+ Indicators such as hematocrit and hemoglobin concentration.

[0048] like Figure 2 As shown in the IP results, compared with the normal group, the model group exhibited significantly decreased oxygen partial pressure and carbon dioxide partial pressure, increased pH, and significantly increased lactate, hematocrit, and hemoglobin concentrations. This indicates that low-pressure hypoxia exposure led to significant hypoxemia, respiratory alkalosis due to hyperventilation, enhanced anaerobic metabolism, and hemoconcentration. Furthermore, the arterial blood potassium levels in the model group were significantly higher. + and Ca 2+ The levels were significantly reduced, suggesting that exposure to low pressure and low oxygen can cause electrolyte homeostasis imbalance.

[0049] After intervention with Compound Manshan White Sugar Syrup, the partial pressure of oxygen in rats increased significantly, while the partial pressure of carbon dioxide and pH returned to normal levels, and the lactate level decreased significantly; simultaneously, the K+ induced by low pressure and hypoxia decreased. + and Ca 2+ The reduction was significantly improved. High-dose compound Manshan white sugar syrup can also reduce hematocrit and hemoglobin concentration levels. Among them, the MSB-H group showed improvement in oxygen partial pressure, reduction in lactic acid, and correction of K+. + and Ca 2+ The compound syrup was superior to the dexamethasone group in terms of all disorders, indicating that it can improve hypobaric hypoxia-induced oxygenation disorders, respiratory alkalosis, lactic acid accumulation, electrolyte disturbances and hemoconcentration.

[0050] 6. Western blot detection Western blot was used to detect the expression of hypoxia-inducible factor-1α and aquaporin 1 in lung tissue. Results are as follows: Figure 3 As shown in AC, the model group showed a significant increase in the expression of the aforementioned proteins, while Compound Manshan White Sugar Syrup significantly reduced their expression. These results suggest that the protective effect of Compound Manshan White Sugar Syrup against hypobaric hypoxia injury may be related to inhibiting the excessive accumulation of hypoxia-inducible factor-1α and regulating the abnormal expression of aquaporins in lung tissue.

[0051] 7. Histopathological examination Lung tissue morphology was observed using hematoxylin-eosin (H&E) staining, and lung injury was scored. The scoring criteria are shown in Table 1. Results are as follows: Figure 3 As shown in DE, the lung tissue structure in the model group was significantly damaged, while Compound Manshan White Sugar Syrup could significantly improve lung tissue damage.

[0052] Table 1 Lung Tissue Injury Scoring Criteria Note: Score = [(20×A) + (14×B) + (7×C) + (7×D) + (2×E)] / (number of regions × 100). The result is a continuous value between 0 and 1 (inclusive).

[0053] 8. Serum biochemical marker detection The levels of serum creatine kinase isoenzymes, aspartate aminotransferase, alanine aminotransferase, creatinine, and total cholesterol were measured using a fully automated biochemical analyzer to evaluate the effects of low-pressure hypoxia exposure and drug intervention on cardiac, hepatic, renal, and lipid metabolism-related indicators.

[0054] The results are as follows Figure 3 As shown in FJ, low-pressure and low-oxygen exposure leads to varying degrees of abnormality in multiple serum biochemical indicators. Compound Manshan White Sugar Syrup can improve these indicators to varying degrees, suggesting that it may alleviate systemic organ stress and metabolic disorders caused by low-pressure and low-oxygen.

[0055] 9. Detection of inflammation-related markers in bronchoalveolar lavage fluid and serum Enzyme-linked immunosorbent assay (ELISA) was used to detect the concentrations of interleukin-17, vascular endothelial growth factor, tumor necrosis factor-α, interleukin-1β, interleukin-6, interleukin-10, and myeloperoxidase in bronchoalveolar lavage fluid and serum, and to evaluate the effects of hypobaric hypoxia exposure and the intervention of compound Manshan white sugar syrup on local and systemic pulmonary inflammatory responses.

[0056] like Figure 4As shown in the AG, compared with the normal group, the levels of interleukin-17, vascular endothelial growth factor, tumor necrosis factor-α, interleukin-1β, interleukin-6, and myeloperoxidase in the bronchoalveolar lavage fluid of the model group were significantly increased, while the level of the anti-inflammatory factor interleukin-10 was significantly decreased, indicating that hypobaric hypoxia exposure can cause significant pulmonary inflammatory response and pro-inflammatory-anti-inflammatory imbalance. After intervention with Compound Manshan White Sugar Syrup, the levels of myeloperoxidase, vascular endothelial growth factor, tumor necrosis factor-α, interleukin-1β, interleukin-6, and interleukin-17 in the bronchoalveolar lavage fluid were significantly decreased, while the level of interleukin-10 was significantly increased. Compared with the dexamethasone positive control group, the MSB-H group showed stronger inhibitory effects in reducing the levels of tumor necrosis factor-α, interleukin-6, and interleukin-17, and the recovery of interleukin-10 was better than that in the dexamethasone group, suggesting that Compound Manshan White Sugar Syrup has superior immunomodulatory activity to dexamethasone in regulating the pro-inflammatory / anti-inflammatory balance in the lungs.

[0057] like Figure 4 As shown in the HN diagram, serum indicators exhibited similar changes. Compared to the normal group, the model group showed significantly elevated levels of serum interleukin-17, vascular endothelial growth factor, tumor necrosis factor-α, interleukin-1β, interleukin-6, and myeloperoxidase, while interleukin-10 levels were significantly decreased. After intervention with Compound Manshan White Sugar Syrup, the aforementioned inflammation-related indicators significantly decreased, and interleukin-10 levels significantly rebounded. These results indicate that Compound Manshan White Sugar Syrup can not only alleviate local lung inflammation but also improve systemic inflammation and immune regulatory imbalance induced by hypobaric hypoxia.

[0058] The results of this embodiment indicate that Compound Manshan White Sugar Syrup can alleviate pulmonary edema induced by hypobaric hypoxia, reduce endothelial barrier permeability, improve oxygenation and blood concentration, and inhibit inflammatory response. Its effects may be related to the regulation of abnormal expression of hypoxia-inducible factor-1α and aquaporin 1, and it has good potential for protection against high-altitude hypobaric hypoxia injury.

[0059] This invention is the first to demonstrate the application value of Compound Manshan White Sugar Syrup in high-altitude hypobaric hypoxia-related diseases. Through multi-target effects, it improves oxygenation, inhibits inflammation, reduces permeability, and regulates the hypoxia-inducible factor-1α / aquaporin pathway, showing good potential for clinical translation.

Claims

1. The use of a pharmaceutical composition in the preparation of a medicament for the prevention and / or treatment of diseases related to high altitude, low pressure, and hypoxia, characterized in that: The pharmaceutical composition is made from the following raw materials: Rhus chinensis, Rhus chinensis, Rhizoma Scutellariae, and Menthol.

2. The application according to claim 1, characterized in that: The pharmaceutical composition is made from the following raw materials in the indicated weight ratios: 800-1000 parts of Rhus chinensis, 500-700 parts of Rhus chinensis, 200-400 parts of Rhizoma Sinensis, and 0.05-0.2 parts of menthol.

3. The application according to claim 2, characterized in that: The pharmaceutical composition is made from the following weight ratio: 900 parts of Rhubarb, 600 parts of Rhus chinensis, 300 parts of Rhizoma Scutellariae, and 0.1 parts of Menthol.

4. The application according to claim 1, characterized in that: The drug is a syrup.

5. The application according to claim 4, characterized in that: The drug in question is Compound Manshan White Sugar Syrup.

6. The application according to claim 1, characterized in that: The drug is used to reduce hypoxia-induced endothelial barrier function damage and improve hypoxia-induced vascular endothelial dysfunction.

7. The application according to claim 1, characterized in that: The drug is used to reduce pulmonary edema and / or lung injury induced by low pressure and hypoxia.

8. The application according to claim 1, characterized in that: The drug is used to improve oxygenation disorders, acid-base imbalances, electrolyte disturbances, and blood concentration caused by low pressure and low oxygen.

9. The application according to claim 1, characterized in that: The drug is used to improve the inflammatory response induced by low pressure and hypoxia and to address the imbalance between pro-inflammatory and anti-inflammatory agents.

10. The application according to claim 1, characterized in that: The high-altitude low-pressure hypoxia-related diseases refer to high-altitude respiratory diseases induced by low pressure and hypoxia, acute mountain sickness, chronic mountain sickness, or hypoxic injury.

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