Application of PBX1 in the preparation of drugs for preventing and treating acute lung injury

Abstract

The present invention is applicable to the field of biomedical technologies, and provides the use of PBX1 in the preparation of drugs for preventing and treating acute lung injury, wherein the coding gene sequence of PBX1 is as shown in SEQ ID No.1. An embodiment of the present invention further provides a TAT-PBX1 recombinant protein and a virus overexpressing the TAT-PBX1 recombinant protein. The present invention also provides a drug for preventing and treating acute lung injury and a medical device for preventing and treating acute lung injury, and the above drug is loaded on the medical device. The present invention constructs a TAT-PBX1 recombinant protein. With the help of the transmembrane effect of TAT, PBX1 can enter cells and play a corresponding antioxidant damage role. TAT-PBX1 can reduce the pathological damage and inflammatory response of the lung tissue of ALI mice, etc. TAT-PBX1 has a protective effect on LPS-induced inflammation.

Description

Technical Field

[0001] The present invention belongs to the technical field of biomedicine, and particularly relates to the application of PBX1 in the preparation of drugs for preventing and treating acute lung injury. Background Art

[0002] As a tiny living organism, viruses widely exist in nature. With the change of the natural environment, they continuously change their genetic and epigenetic information in an evolutionary way to adapt to environmental changes so as to survive. With the continuous expansion of the scope of human social activities, viruses originally present in natural environment organisms are very likely to invade the human body, thus causing serious harm to the population and even leading to the occurrence of public health emergencies. For example, acute and severe lung injuries caused by acute respiratory viruses such as MERS, SARS, and COVID-19 have caused great harm to humans and seriously endangered human health. A series of antiviral drugs have been developed in the prior art, such as ribavirin, acyclovir, ganciclovir, oseltamivir, etc., for resisting respiratory virus infections and have achieved certain clinical effects. However, the efficacy of antiviral drugs depends to a large extent on the virus type and the specific condition of the patient. Whether these known antiviral drugs have a definite efficacy against unknown novel respiratory viruses is currently unknown. The research and development of respiratory virus vaccines has always been a hot spot and focus in the field of biomedicine. However, respiratory viruses mutate rapidly. Developing vaccines against unknown novel respiratory viruses has a long cycle and is difficult to meet the rescue needs. Moreover, it is impossible to talk about whether the existing respiratory virus vaccines can produce an immune response to novel respiratory viruses.

[0003] In view of the fact that acute and severe lung injuries caused by acute respiratory viruses such as MERS, SARS, and COVID-19 have a common pathogenesis, that is, after the virus enters the respiratory tract, it induces the body to produce an excessive immune response and a severe inflammatory response, causing large-area necrosis of the lungs of the infected person, and ultimately leading to the death of the patient due to respiratory failure. Therefore, how to inhibit inflammatory necrosis is a problem that needs to be solved in the prevention and treatment of acute lung injury. Summary of the Invention

[0004] The purpose of the embodiment of the present invention is to provide the application of PBX1 in the preparation of drugs for preventing and treating acute lung injury, aiming to solve the problems raised in the above background art.

[0005] The embodiment of the present invention is implemented as follows. The application of PBX1 in the preparation of drugs for preventing and treating acute lung injury, wherein the coding gene sequence of PBX1 is as shown in SEQ ID No.1.

[0006] Another object of the embodiments of the present invention is to provide a TAT-PBX1 recombinant protein. The preparation of the recombinant protein comprises the following steps: amplifying the coding gene of PBX1 by PCR method, connecting the PCR product to a cloning vector by cloning, and picking the correctly connected white clone by blue-white screening; after identification by colony PCR, enzyme digestion and gene sequencing, inserting the PBX1 coding gene fragment in the positive clone into the prokaryotic expression vector pTAT-HA by enzyme digestion and T4 ligation, then transferring it into a prokaryotic expression strain, and obtaining a positive transformant through ampicillin resistance screening; activating in an expression medium, performing enlarged culture, and centrifuging to collect the precipitate; placing the precipitate in a lysis solution for ultrasonic disruption and dissolution, centrifuging to collect the supernatant, filtering, purifying, then performing renaturation by pulse dilution, dialyzing and ultrafiltering the renaturation solution to obtain the TAT-PBX1 recombinant protein.

[0007] Another object of the embodiments of the present invention is to provide a virus overexpressing the TAT-PBX1 recombinant protein, and the virus vector is one of a lentivirus, a retrovirus, an adenovirus, and an adeno-associated virus.

[0008] Another object of the embodiments of the present invention is to provide a drug for preventing and treating acute lung injury, and the drug comprises the TAT-PBX1 recombinant protein or the virus overexpressing the TAT-PBX1 recombinant protein.

[0009] Preferably, the drug further comprises excipients.

[0010] Another object of the embodiments of the present invention is to provide a medical device for preventing and treating acute lung injury, and the above drug is loaded on the medical device.

[0011] Application of PBX1 provided by the embodiments of the present invention in the preparation of drugs for preventing and treating acute lung injury. The pre-B-cell leukemia homeobox 1 (PBX1) is one of the members of the homeobox gene family. It encodes the transcription factor PBX1, which is widely expressed in various tissues. Its functions include aspects such as self-renewal, proliferation, and differentiation of stem cells. PBX1 not only plays an important role in the process of biological development, but also has a regulatory role in many organs. In terms of the nervous system, PBX1 participates in neurogenesis and is a starting factor for neurogenesis in the subventricular zone of the adult cerebral ventricle. During the development of NK cells, PBX1 plays a key role by directly binding to the Nfil3 promoter. PBX1 can also promote proliferation and inhibit apoptosis, thus inducing abnormal heart development, and it is essential for bone formation, adrenal gland, pancreas, urogenital development, kidney formation, and maintaining hematopoiesis. However, as a transcription factor, due to its large molecular weight, PBX1 cannot enter cells through the cell membrane. The embodiments of the present invention construct the TAT-PBX1 recombinant protein. With the help of the transmembrane effect of TAT, PBX1 can enter cells and play a corresponding antioxidant damage role. An acute lung injury mouse model is established by intratracheal instillation of lipopolysaccharide (LPS) to simulate severe lung injury induced by an unknown novel acute respiratory virus, and the effects of TAT-PBX1 on reducing pathological damage and inflammatory response in the lung tissue of acute lung injury (ALI) mice are observed. An in vitro model is established by stimulating human alveolar epithelial cells A549 with LPS, and the protective effect of TAT-PBX1 on LPS-induced inflammation is observed. Description of the Drawings

[0012] Figure 1 It is the plasmid map of TAT-PBX1 provided by the embodiments of the present invention;

[0013] Figure 2 a shows the construction of the prokaryotic expression system of TAT-PBX1 provided by the embodiments of the present invention and the results of denaturation, purification, and renaturation of the recombinant protein; Figure 2 b shows that His-tag can be detected in the lung tissue of mice 3 hours after intraperitoneal injection of TAT-PBX1 (2.5 mg / Kg), indicating that TAT-PBX1 can enter the lung tissue.

[0014] Figure 3 a, b, and c respectively show the results of the body weight, organ index, and wet / dry weight ratio of the lung tissue of mice provided by the embodiments of the present invention (CON is the control group; LPS is the model group; before-L, before-M, before-H are the low, medium, and high dose groups of TAT-PBX1 intraperitoneally injected before LPS induction; after-L, after-M, after-H are the low, medium, and high dose groups of TAT-PBX1 intraperitoneally injected after LPS induction);

[0015] Figure 4 The HE staining results of mouse lung tissues provided by the embodiments of the present invention;

[0016] Figure 5 a shows the detection results of the protein concentration in the alveolar lavage fluid of mice in each group provided by the embodiments of the present invention, Figure 5 b shows the total cell count results of the alveolar lavage fluid of mice in each group.

[0017] Figure 6 a shows the detection results of inflammatory factors in the alveolar lavage fluid of mice in each group provided by the embodiments of the present invention, Figure 6 b shows the detection results of inflammatory factors in the serum of mice in each group.

[0018] Figure 7 The ELISA detection of inflammatory factors in human alveolar epithelial cells provided by the embodiments of the present invention;

[0019] Figure 8 The detection of ROS in human alveolar epithelial cells by flow cytometry provided by the embodiments of the present invention;

[0020] Figure 9 The detection of mitochondrial membrane potential in human alveolar epithelial cells by flow cytometry provided by the embodiments of the present invention;

[0021] Figure 10 The Western Blot protein detection results of mouse lung tissues provided by the embodiments of the present invention. Detailed implementation manners

[0022] In order to make the objectives, technical solutions and advantages of the present invention clearer and more understandable, the following further describes the present invention in detail with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention.

[0023] The following describes the specific implementation of the present invention in detail with reference to specific embodiments.

[0024] Example 1. Preparation of TAT-PBX1 recombinant protein, including the following steps:

[0025] The coding gene of PBX1 (whose sequence is shown in SEQ ID No.1) was amplified by PCR method. The PCR product was ligated to the cloning vector pT-EASY through T-A cloning. Subsequently, the correct ligated white clones were picked by blue-white screening; after identification by colony PCR, enzyme digestion and gene sequencing, the PBX1 coding gene fragment in the positive clone was inserted into the prokaryotic expression vector pTAT-HA by enzyme digestion and T4 ligation, and then transferred into the prokaryotic expression strain Rosetta(DE3). Positive transformants were obtained through ampicillin resistance screening. It was activated overnight at 37°C in the expression medium, expanded and cultured, and the precipitate was collected by centrifugation; the precipitate was placed in the lysis solution and dissolved by ultrasonic disruption, centrifuged at 12,000 g for 30 min, and the supernatant was collected; after the supernatant was filtered through a 0.45 μm filter, it was purified by nickel column affinity chromatography, then renatured by pulse dilution, and then the renatured solution was dialyzed and ultrafiltered to obtain a high-concentration recombinant protein of TAT-PBX1. The plasmid map of TAT-PBX1 is as Figure 1 shown. The DNA sequence of PBX1 was added to the C-terminus of the TAT peptide in the plasmid vector pTAT-HA, which contains an N-terminal His6 tag for purification and an HA tag for distinguishing TAT and PBX1;

[0026] The specific purification steps of the recombinant protein of TAT-PBX1 are as follows: Using a Ni2+-NTA-agarose column, after equilibration with the binding buffer, the bacterial supernatant was loaded onto the chromatography column, the chromatography column was rinsed with the washing buffer, and then the recombinant protein of TAT-PBX1 bound to the chromatography column was eluted with the elution buffer;

[0027] The specific renaturation steps of the recombinant protein of TAT-PBX1 are as follows: According to a dilution ratio of 1:1-20, the eluted sample was renatured in the renaturation buffer. After renaturation, the supernatant was introduced into a dialysis bag and dialyzed overnight with phosphate buffer at 4°C. After that, a 30-kDa ultrafiltration tube was used to concentrate the denatured protein, and a BCA protein detection kit was used to measure the concentration of the recombinant protein.

[0028] Example 2: Experiment on TAT-PBX1 alleviating acute lung injury:

[0029] In vitro experiment: Cells were modeled with LPS. The groups were blank control group, TAT-PBX1 recombinant protein group, LPS group, and LPS + TAT-PBX1 recombinant protein group. Inflammatory factors in the cell supernatant were detected by ELISA kit, cell ROS was detected by DCFH-DA probe, and cell mitochondrial membrane potential was detected by JC-1;

[0030] In vivo experiment: 6-8 week old male SPF grade C57BL / 6 mice were housed at a constant temperature of 22°C and constant humidity in a quiet environment. The mice were randomly divided into 5 groups: blank control group, LPS group, low-dose TAT-PBX1 recombinant protein group, medium-dose TAT-PBX1 recombinant protein group, and high-dose TAT-PBX1 recombinant protein group. The mice were intraperitoneally injected with low (2.5 mg / kg), medium (5 mg / kg), and high (10 mg / kg) doses of TAT-PBX1 recombinant protein, respectively. Three hours later, LPS was instilled into the trachea to establish the model. Twenty-four hours later, the mice were killed by cervical dislocation, and the required organs and samples were obtained for pathological observation, ELISA detection of inflammatory factors, detection of protein concentration and total cell number in bronchoalveolar lavage fluid, flow cytometry detection of ROS and mitochondrial membrane potential in lung tissue, and Western blot detection of related protein expression.

[0031] Statistical analysis: All data are expressed as mean ± standard deviation. Statistical analysis and statistical graph generation were performed using GraphPad Prism 8 software. For intergroup comparisons, if the data conformed to a normal distribution, one-way analysis of variance (ANOVA) was used, and multiple comparisons between groups were performed using the least significant difference (LSID) test. If the data had unequal variances, the Kruskal-Wallis test was used, with an a-0.05 test level. p < 0.05 was considered statistically significant, and p < 0.01 was considered statistically significant.

[0032] The construction of TAT-PBX1 prokaryotic expression system and the results of denaturation, purification and renaturation of recombinant protein are shown in Figure 2. Figure 2 As shown in a, based on the Coomassie Brilliant Blue results of the bacterial solution (also called the starting solution, Start), flowthrough, wash solution, and elution solution, it was demonstrated that the purity of the purified TAT-PBX1 was greater than 90%, the molecular weight was correct, and it could be successfully detected; Figure 2 b: Three hours after intraperitoneal injection of TAT-PBX1 (2.5 mg / Kg), His-tag was detected in the lung tissue of mice, indicating that TAT-PBX1 can enter the lung tissue.

[0033] Result analysis:

[0034] TAT-PBX1 recombinant protein alleviates LPS-induced acute lung injury in mice:

[0035] First, the effect of TAT-PBX1 recombinant protein was evaluated by observing the differences in body weight, organ index and lung tissue wet-to-dry weight ratio of each group of mice. Figure 3 As shown, Figure 3a shows the body weights of mice in each group. Compared with the control group, the body weights of mice in the LPS group were significantly decreased, while those of mice in the before-H group were significantly increased; Figure 3 b shows the organ index of the lung tissues of mice in each group. Compared with the control group, the organ index of the lung tissues of mice in the LPS group was significantly increased, while that of mice in the before-H group was significantly decreased; Figure 3 c shows the wet / dry weight ratio of the lung tissues of mice in each group. Compared with the control group, the wet / dry weight ratio of the lung tissues of mice in the LPS group was significantly increased, while those of mice in the before-M, before-H, and after-H groups were significantly decreased. The results of the organ index and wet / dry weight ratio of the lung tissues indicate that LPS causes a certain degree of pulmonary edema in mice, while the TAT-PBX1 recombinant protein can reduce pulmonary edema;

[0036] By observing the pathological sections, the recovery of the TAT-PBX1 recombinant protein for LPS-induced lung tissue injury in mice was explored. Figure 4 This is the pathological condition of the lung tissues after intraperitoneal injection of the TAT-PBX1 recombinant protein before and after LPS-induced acute lung injury in mice. The results of HE staining of liver tissues were observed under an optical microscope. The alveolar walls of mice in the control group were thinner, with only a small amount of inflammatory cell infiltration in the alveolar cavity, no bleeding points, and the lung tissue structure was intact; while the alveolar walls of LPS mice were thickened, accompanied by a large amount of inflammatory cell infiltration, and the lung tissue structure was severely damaged; whether the TAT-PBX1 was injected first or later, the alveolar cell structure had a relatively obvious recovery, the inflammatory cell infiltration was significantly reduced, and the alveolar walls became thinner;

[0037] By detecting the protein concentration and total cell number in the bronchoalveolar lavage fluid of mice, the permeability of the lung tissues of mice was evaluated, and the results are as Figure 5 shown. Figure 5 a shows the detection results of the protein concentration in the bronchoalveolar lavage fluid of mice in each group. Compared with the control group, the protein concentration in the bronchoalveolar lavage fluid of mice in the LPS group was significantly increased, while that of mice in the before-H group was significantly decreased; Figure 5 b shows the results of the total cell count in the bronchoalveolar lavage fluid of mice in each group. Compared with the control group, the total cell number in the bronchoalveolar lavage fluid of mice in the LPS group was significantly increased, while that of mice in the before-H group was significantly decreased. The above results indicate that LPS leads to an increase in the permeability of the lung tissues of mice and a dysfunction of the alveolar capillary barrier, while the TAT-PBX1 recombinant protein can reduce lung injury;

[0038] The ELISA method was used to detect the levels of inflammatory factors in the bronchoalveolar lavage fluid and serum of mice to evaluate the effect of the TAT-PBX1 recombinant protein on the inflammatory response, and the results are Figure 6 shown. Figure 6a shows the detection results of inflammatory factors in the bronchoalveolar lavage fluid of mice in each group. Compared with the control group, the levels of inflammatory factors in the bronchoalveolar lavage fluid of mice in the LPS group were significantly increased, while the levels of inflammatory factors in the bronchoalveolar lavage fluid of mice in the before-H group were significantly decreased; Figure 6 b shows the detection results of inflammatory factors in the serum of mice in each group. Compared with the control group, the levels of inflammatory factors in the serum of mice in the LPS group were significantly increased, while the levels of inflammatory factors in the serum of mice in the before-H group were significantly decreased. The above results indicate that LPS induced lung tissue and systemic inflammatory responses in mice, while the TAT-PBX1 recombinant protein could reduce lung tissue and systemic inflammation in mice.

[0039] The TAT-PBX1 recombinant protein can reverse the changes in inflammation, ROS, and mitochondrial membrane potential in LPS-stimulated human alveolar epithelial cells:

[0040] An in vitro model of acute lung injury was constructed by stimulating human type II alveolar epithelial cells A549 with LPS. Inflammatory factors were detected by ELISA, and the levels of ROS and mitochondrial membrane potential in human alveolar epithelial cells were detected by flow cytometry respectively to evaluate whether the TAT-PBX1 recombinant protein could reverse the changes in inflammation, ROS, and mitochondrial membrane potential induced by LPS in human alveolar epithelial cells;

[0041] Figure 7 The results of ELISA detection of inflammatory factors are shown. Compared with the control group, the inflammatory factors in the LPS group were significantly increased, while the inflammatory factors in the before-H group were significantly decreased, indicating that the TAT-PBX1 recombinant protein could reduce the inflammatory response; Figure 8 The results of ROS in human alveolar epithelial cells are shown. Compared with the control group, the ROS in the LPS group were significantly increased, while the ROS in the before-H group were significantly decreased, indicating that the TAT-PBX1 recombinant protein could reduce ROS; Figure 9 The results of mitochondrial membrane potential in human alveolar epithelial cells are shown. Compared with the control group, the mitochondrial membrane potential in the LPS group was significantly decreased, while the mitochondrial membrane potential in the before-H group was significantly recovered, indicating that the TAT-PBX1 recombinant protein could restore the mitochondrial membrane potential.

[0042] The TAT-PBX1 recombinant protein reduces apoptosis in mouse lung tissue:

[0043] The expression of apoptosis-related proteins was detected by Western Blot, and the results are as follows Figure 10As shown, compared with the control group, the level of Cleaved Caspase3 in the LPS group was significantly increased, and the difference was statistically significant (p < 0.05). The expression levels of apoptosis-related proteins in the low, medium, and high-dose groups of TAT-PBX1 were significantly downregulated compared with those in the LPS group. Compared with the control group, the level of γH2A.X in the LPS group was significantly increased, and TAT-PBX1 significantly downregulated the protein expression level of γH2A.X, with a statistically significant difference (p < 0.05). In addition, TAT-PBX1 could significantly upregulate the protein levels of AMPKγ2, PGC-1α, and TFAM (p < 0.05), indicating that PBX1 might promote mitochondrial biogenesis. It can be seen that the recombinant protein TAT-PBX1 might alleviate LPS-induced DNA damage and apoptosis in lung tissue by regulating the AMPKγ2 / PGC-1α / TFAM pathway.

[0044] In summary, PBX1 slows down cell senescence and inhibits apoptosis by reducing the accumulation of reactive oxygen species and inhibiting mitochondrial damage mediated by inflammation and overactive immune responses. Cell-penetrating peptides (CPPs) have been used to deliver a variety of molecules, especially the delivery of large-molecular-weight active proteins from outside the cell to inside the cell, such as protamine, TAT peptide, or R9. Among them, the transcriptional transactivator (TAT) is a peptide derived from the human immunodeficiency virus and is one of the most commonly used cell-penetrating peptides. When TAT binds to cells, it can enhance the uptake of proteins by cells.

[0045] The PBX1 provided in the embodiments of the present invention exists in the culture medium of cells (such as human cells like mesenchymal stem cells, neural crest stem cells, pigment stem cells, and fibroblasts, etc.). To facilitate membrane penetration, PBX1 usually also includes a cell-penetrating peptide, such as TAT.

[0046] The overexpressed TAT-PBX1 cells or culture supernatants provided in the embodiments of the present invention are achieved by overexpressing the TAT-PBX1 protein through lentivirus infection of cells. Due to the TAT cell-penetrating peptide, the PBX1 protein contained in the cell culture supernatant can enter the cells.

[0047] The recombinant protein TAT-PBX1 provided in the embodiments of the present invention is an exogenous protein expressed by Escherichia coli, yeast, or CHO cells. Because the TAT cell-penetrating peptide enhances the uptake of proteins by cells such as alveolar epithelial cells, neurons, and mesenchymal stem cells, PBX1 can cross the cell membrane and enter the nucleus. And the experimental results show that the prokaryotically expressed TAT-PBX1 still has transcriptional activity after entering the nucleus.

[0048] The TAT-PBX1 recombinant protein provided by the embodiments of the present invention is packaged with lentivirus, adenovirus, adeno-associated virus, retrovirus, etc., and then transduced into human cells, including but not limited to mesenchymal stem cells, neural crest stem cells, pigment stem cells, fibroblasts, etc.;

[0049] Upregulating PBX1 can significantly reduce the excessive accumulation of intracellular ROS, mitochondrial damage and apoptosis caused by LPS. Lentivirus infection of mesenchymal stem cells overexpressing TAT-PBX1 can upregulate the expression of PBX1 protein.

[0050] After intraperitoneal injection or gastrointestinal administration, the TAT-PBX1 recombinant protein enters the mouse lung tissue and other tissues;

[0051] Using PBX1 or TAT-PBX1 as an active ingredient for the prevention and treatment of acute lung injury. Specifically, mixing PBX1 or TAT-PBX1 with other excipients to prepare a drug (preparation) for the prevention and treatment of acute lung injury;

[0052] Pharmaceutical excipients can be those commonly used in various preparations, such as: but not limited to isotonic agents, buffers, flavoring agents, excipients, fillers, binders, disintegrants and lubricants, etc.; they can also be selected for adaptation to substances, such as: emulsifiers, solubilizers, bacteriostatic agents, analgesics and antioxidants, etc. Such excipients can effectively improve the stability and solubility of the compounds contained in the composition or change the release rate and absorption rate of the compounds, etc., thereby improving the metabolism of various compounds in the body and further enhancing the administration effect of the composition;

[0053] In aqueous injection solutions, excipients generally include isotonic agents and buffers, as well as necessary emulsifiers (such as Tweeen-80, Pluronic and Poloxamer, etc.), solubilizers and bacteriostatic agents, etc. In addition, it also includes other pharmaceutically acceptable pharmaceutical excipients, such as: antioxidants, pH regulators and analgesics, etc.;

[0054] Excipients for preparing liquid preparations generally include solvents, water, oils (such as fatty acids), emulsifiers, and necessary preservatives, etc.;

[0055] Various excipients and the culture medium supernatant prepared in the embodiments of the present invention are made into dosage forms beneficial for drug delivery, such as: but not limited to aqueous injection, nasal drops, eye drops, powder for injection, powder, patch, suppository, emulsion, cream, gel, aerosol, spray, powder inhaler, sustained-release agent, controlled-release agent, etc. In addition, excipients used for achieving specific drug delivery purposes or methods, such as: sustained-release drug delivery, controlled-release drug delivery, pulsed drug delivery, etc., can also be used, such as: but not limited to gelatin, albumin, chitosan, polyether and polyester polymers, such as: but not limited to, polyethylene glycol, polyurethane, polycarbonate and their copolymers, etc. The main manifestations of the so-called "beneficial for drug delivery" include: but not limited to improving the therapeutic effect, increasing the bioavailability, reducing the toxic and side effects, and improving the patient compliance, etc.;

[0056] In addition, a drug-containing medical device made by combining a drug and a medical device can also be prepared. For example, a dressing containing TAT-PBX1 in the embodiments of the present invention, where TAT-PBX1 in the embodiments of the present invention is loaded or coated on a material as an active ingredient to be used for preparing a medical device for preventing and treating acute lung injury. Common stent materials such as: PLA, PLGA, GelMA and metals, etc., and micro needles and their micro needle arrays are made by mixing with a biocompatible biodegradable material, or loaded in metal micro needles to make a micro needle chip. When the micro needles pierce into the skin, TAT-PBX1 is released into the epithelial tissue, enters the blood, and reaches the damaged organ site to prevent and treat acute lung injury.

[0057] The above are only the preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. Use of PBX1 in the preparation of drugs for preventing and treating acute lung injury, characterized in that, The coding gene sequence of PBX1 is shown in SEQ ID No.1.

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