Active peptide for improving brain injury and application thereof

Abstract

The application belongs to the technical field of active peptides, and particularly relates to an active peptide with the function of improving brain injury and application thereof, wherein the amino acid sequence of the active peptide is shown as SEQ ID NO. 1, and the active peptide can improve brain injury and has a good promoting effect on the prognosis of patients with brain injury.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of active peptides, in particular, the present application relates to an active peptide with improved brain injury function and its application. BACKGROUND

[0002] Brain injury is caused by head and face trauma, which leads to brain tissue damage. It is clinically common and usually caused by trauma with acute onset. Typical symptoms include headache, disturbance of consciousness, and intracranial hemorrhage. Generally, it needs conservative treatment or surgical treatment. The prognosis of mild patients is good, and severe patients often have varying degrees of neurological deficits (limb paralysis, unclear speech, sensory disturbance, etc.), and the prognosis is poor.

[0003] The prognosis of brain injury is closely related to the severity of the injury, the age and health status of the patient, timely treatment and rehabilitation measures, etc. Generally speaking, the prognosis of mild brain injury is more optimistic, while the prognosis of severe brain injury is more severe. The prognosis of mild brain injury is usually good, and patients can fully recover after receiving appropriate treatment. Mild brain injury is usually manifested as transient loss of consciousness or headache, dizziness, etc. after head injury, and usually does not leave obvious sequelae. The prognosis of severe brain injury is often complex, and severe brain injury can have a long-term impact on the patient's physical and cognitive function. Patients with severe brain injury may have long-term loss of consciousness, memory loss, language impairment, and severe sequelae such as limb disability. At this time, the patient needs to receive comprehensive rehabilitation treatment and may need long-term care and support.

[0004] At present, common prognosis drugs for brain injury include isotonic whole protein formula (polypeptide) and the like. Peptides are helpful for brain nerve repair, can help activate the nervous system, are important components of brain tissue structure, can provide raw materials for the physiological activity of brain cells, and can improve the excitability of brain cells. Peptides have a certain effect on activating the nervous system, so it is necessary to supplement peptides during the repair process when brain nerve damage occurs, which can help speed up the recovery of nerve function. In addition, peptides are rich in lipids and unsaturated fatty acids, which are important components of the brain, so peptides can promote the repair of brain nerves. In addition, peptides can provide sufficient raw materials for the physiological activity of brain cells, thereby promoting the development and functional activity of brain cells and helping the repair of brain nerves. In addition, peptides can improve the excitability of brain cells, help the faster recovery of fatigued or damaged brain cells, and prevent the occurrence of sequelae of neurological dysfunction, so peptides are helpful for brain nerve repair.

[0005] However, the commonly used peptides at present are mostly whole peptides, which often have poor effect in the use of patients, and it is still necessary to find a small molecule peptide that can effectively treat brain injury. SUMMARY

[0006] In view of the above, the present application provides an active peptide having an improved brain injury function, which can be used to improve the prognosis of patients with brain injury.

[0007] In a first aspect, the present application provides an active peptide having an improved brain injury function, the amino acid sequence of which is shown in SEQ ID NO. 1.

[0008] In a second aspect, the present application provides a nucleic acid molecule encoding the active peptide according to the first aspect, or reverse complementary to the nucleotide sequence encoding the active peptide of claim 1.

[0009] In a third aspect, the present application provides a recombinant vector containing the nucleic acid molecule of the second aspect and capable of expressing the active peptide of the first aspect.

[0010] In a fourth aspect, the present application provides a host cell having the nucleic acid molecule of the second aspect incorporated into its genome and capable of expressing the active peptide of the first aspect.

[0011] In a fifth aspect, the present application provides the use of the active peptide of the first aspect, the nucleic acid molecule of the second aspect, the recombinant vector of the third aspect, or the host cell of the fourth aspect in the preparation of a medicament for treating a brain injury-related disease, wherein the brain injury-related disease includes, but is not limited to, stroke, brain trauma, and neurodegenerative disease.

[0012] In a sixth aspect, the present application provides a medicament for treating a brain injury-related disease, comprising the active peptide of the first aspect and a pharmaceutically acceptable excipient.

[0013] The medicament according to the aforementioned sixth aspect, wherein the excipient comprises one or more of a diluent, a preservative, a buffer, a disintegrant, an antioxidant, a suspending agent, a coloring agent. BRIEF DESCRIPTION OF DRAWINGS

[0014] The preferred features, embodiments, and variations of the present application can be seen from the following detailed description, which provides sufficient information for those skilled in the art to perform the present application. The detailed description should not be regarded as limiting the scope of the foregoing summary in any way.

[0015] Figure 1 is a schematic diagram of the comparison of the fluorescence values of zebrafish NSE after treatment of each sample in Example 5. DETAILED DESCRIPTION

[0016] The application will be described in further detail below with reference to specific embodiments. The embodiments are presented by way of illustration of the application, and are not intended to limit the scope of the application. Various modifications to the application can be made by those skilled in the art upon reading the description of the application. Such equivalent modifications are intended to fall within the scope of the application as defined by the appended claims.

[0017] Related Terms

[0018] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. The terminology used in the description of the application herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the application. As used herein, the term "and / or" includes any and all combinations of one or more of the associated listed items.

[0019] "Small molecule peptide" is a biochemical substance between amino acids and proteins, which has smaller molecular weight than proteins and larger molecular weight than amino acids. Small molecule peptides have simple structure and small molecular weight, can quickly penetrate the small intestine mucosa for absorption without the need for further digestion and energy consumption, and have the characteristics of 100% absorption. Small molecule peptides can penetrate the skin barrier, blood-brain barrier, placental barrier and gastrointestinal mucosal barrier to directly enter cells. Therefore, the absorption, transformation and utilization of small molecule peptides are efficient and complete.

[0020] "Active peptide" refers to a peptide molecule with specific biological activity, the function of which is determined by its amino acid sequence and structure. The active peptide involved in the present application has a small molecular weight and belongs to small molecule peptides.

[0021] "Vector" refers to a nucleic acid carrier tool into which a polynucleotide can be inserted. When the vector can make the inserted polynucleotide coding protein obtain expression, the vector is called an expression vector. The vector can be introduced into a host cell by transformation, transduction or transfection, so that the genetic material elements carried by the vector can be expressed in the host cell. The vector is well known to those skilled in the art, including but not limited to: plasmid; phagemid; cosmid; artificial chromosome, such as yeast artificial chromosome (YAC), bacterial artificial chromosome (BAC) or P1-derived artificial chromosome (PAC); bacteriophages such as lambda phage or M13 phage, and animal viruses, etc. Animal viruses that can be used as vectors include but are not limited to, retrovirus (including lentivirus), adenovirus, adeno-associated virus, herpes virus (such as herpes simplex virus), poxvirus, baculovirus, papillomavirus, papovavirus (such as SV40).

[0022] The "host cell" refers to a cell that can be used for introducing a vector, including but not limited to a prokaryotic cell such as Escherichia coli or Bacillus subtilis, a fungal cell such as a yeast cell or Aspergillus, an insect cell such as S2 Drosophila cell or Sf9, or an animal cell such as fibroblast cell, CHO cell, COS cell, NSO cell, HeLa cell, BHK cell, HEK 293 cell or human cell.

[0023] The small molecule peptide constructed by the screening method of the present application can induce apoptosis and proliferation of brain tissue cells, improve damaged brain tissue, and reduce the expression of neuron-specific enolase.

[0024] The nucleic acid molecule of an embodiment of the present application encodes the small molecule peptide as described above, i.e., the coding strand, or is reverse complementary to the nucleotide sequence encoding the small molecule peptide as described above, i.e., the antisense strand.

[0025] It can be understood that, due to the degeneracy of codons, there are multiple forms of nucleic acid sequences capable of expressing the same small molecule peptide, and those skilled in the related art can determine the nucleic acid sequence by a codon table and further optimize the codons to improve the expression efficiency, etc.

[0026] The recombinant vector of an embodiment of the present application contains the nucleotide sequence of the nucleic acid molecule as described above.

[0027] It can be understood that the vector can also contain regulatory elements commonly used in genetic engineering, such as enhancers, promoters, etc., and other expression control elements (such as transcription termination signals, or polyadenylation signals and poly U sequences, etc.).

[0028] The host cell of an embodiment of the present application has the nucleic acid molecule as described above incorporated into its genome.

[0029] It can be understood that the small molecule peptide, nucleic acid molecule, recombinant vector or host cell as described above can all be applied to the preparation of a product for treating brain injury-related diseases.

[0030] The preparation method of the small molecule peptide as described above of an embodiment of the present application can artificially synthesize the small molecule peptide, or use the host cell as described above to express the small molecule peptide.

[0031] The drug for brain injury-related diseases of an embodiment of the present application includes the small molecule peptide as described above, and a pharmaceutically acceptable excipient.

[0032] In a specific example, the excipient includes one or more of a diluent, a preservative, a buffer, a disintegrant, an antioxidant, a suspending agent, a coloring agent and an excipient.

[0033] In one particular example, the diluent is selected from one or more of polyethylene glycol, propylene glycol, vegetable oil, and mineral oil. In one particular example, the preservative is selected from one or more of sorbic acid, methyl sorbate, methyl paraben, ethyl paraben, propyl paraben, butyl paraben, benzyl paraben, sodium methyl paraben, benzoic acid, and benzyl alcohol. In one particular example, the buffering agent is selected from one or more of sodium phosphate monobasic, sodium phosphate dibasic, sodium citrate, sodium tartrate, and sodium acetate. In one particular example, the disintegrant is selected from one or more of crosscarmellose sodium, sodium carboxymethyl starch, cross-linked polyvinyl pyrrolidone, or low-substituted hydroxypropyl cellulose. In one particular example, the antioxidant is selected from one or more of ethylenediaminetetraacetic acid, disodium edetate, butylated hydroxytoluene, glycine, inositol, ascorbic acid, sodium ascorbate, lecithin, malic acid, hydroquinone, citric acid, succinic acid, and sodium metabisulfite. In one particular example, the suspending agent is selected from one or more of beeswax, ethyl hydroxyethyl cellulose, chitin, chitose, methyl cellulose, carboxymethyl cellulose, agar, hydroxypropyl methyl cellulose, and xanthan gum. In one particular example, the coloring agent is selected from one or more of carbon black, iron black, iron brown, iron red, and titanium dioxide. In one particular example, the excipient is selected from one or more of mannitol, dextrose, lactose, dextran, dextranose, and sodium chloride.

[0034] The experimental methods used in the following examples are conventional unless otherwise specified. The materials, reagents, etc. used in the following examples are commercially available unless otherwise specified.

[0035] Example 1: Preparation of small molecule peptides

[0036] A method for preparing brain polypeptides and brain small molecule peptides by enzymatic hydrolysis of porcine brain, comprising the following steps:

[0037] Step 1: Fresh porcine brain or thawed frozen porcine brain is washed with purified water, and the fascia and blood vessels are removed. The porcine brain is mixed with purified water at a ratio of 1:1.5, and then ground and homogenized with a colloid mill. After the tissue is basically broken, the homogenization is adjusted to a finer fineness, and the homogenization cycle is 5 minutes / batch. Then, 1.3 times the purified water of the homogenate is added for continued homogenization for 5 minutes. The homogenized brain slurry of each batch is mixed uniformly, and the pH value is adjusted to 9.5 with potassium hydroxide solution. The coarsest mesh size is 100 mesh, and the finer mesh size is 150 mesh.

[0038] Step 2: The adjusted brain plasma homogenate is placed in a microwave tank with stirring device, the temperature is controlled at 60℃, and the microwave is applied for 20 minutes, and the temperature is kept for 15 minutes; the frequency of the microwave tank is 3300 MHz, and the power is 25 kW; the microwave treated homogenate is discharged, and the protein and lipid are separated by a butterfly high-speed centrifuge twice at 38℃; the light liquid discharged in the first centrifugation is controlled to be 42%, and the light liquid is discharged after the first centrifugation; then the microwave is applied for 20 minutes, and the second centrifugation is performed; the light liquid obtained by the second centrifugation is the phospholipid solution, and the concentrated liquids obtained by the two centrifugations are mixed; the rotating speed of the first centrifugation is 9000 rpm, and the rotating speed of the second centrifugation is 12000 rpm; the temperature of the homogenate in the second centrifugation is not lower than 38℃;

[0039] Step 3: The mixed concentrated liquid obtained in step 2 is adjusted to pH 5.0 by dilute hydrochloric acid, so that the protein is in the form of cloud-like large pieces and is separated, then the liquid is removed by a 250-mesh filter centrifuge, the filter residue is collected, and the brain separated protein is obtained; the collected filter residue is dissolved in 2 times the amount of pure water based on the wet filter residue to obtain a solution with a concentration of 5%, and the pH value is adjusted to 9.0, then trypsin (5000 u / g) with a mass of 4.5% of the brain separated protein is added for further homogenization circulation; when the pH value decreases to about 7.5 again, the alkali is supplemented to adjust the pH value to 8.6, and the slurry is discharged after circulating for 3 minutes;

[0040] Step 4: The slurry obtained in step 3 is sent to the microwave for pre-detection of the pH value, when the pH value is less than 7, the pH value is adjusted to 8.2 by supplementing alkali, microwave-assisted enzymatic hydrolysis is performed, and the temperature is kept for 15 minutes to inactivate the enzyme activity; the enzyme hydrolysis liquid with inactivated enzyme activity is discharged, when the temperature of the enzyme hydrolysis liquid decreases to less than 40℃, 1.5% chitosan solution dissolved in 15% acetic acid is added under stirring to adjust the pH value to 4.8, so as to precipitate the unhydrolyzed brain protein, phospholipid and other macromolecular impurities; the precipitate is removed by centrifugal filtration with a 200-mesh filter cloth; the centrifugal liquid is filtered by a 0.25-micron hollow fiber membrane, and the filtrate is filtered by an ultrafiltration membrane with a molecular weight interception of 10000 Da, and the permeate is the pig brain polypeptide solution; if only polypeptide is prepared, the solution is reduced pressure concentrated, and then freeze-dried to obtain polypeptide powder;

[0041] Step 5: The polypeptide solution is filtered by a nanofiltration membrane with a molecular weight interception of 1200 Da, and the filtrate is concentrated by a reverse osmosis membrane, and the concentrated liquid is frozen and dried to obtain small molecular brain peptides.

[0042] Example 2 LC-MS / MS separation and identification

[0043] LC-MS / MS was used to determine the amino acid sequence and molecular weight of the small molecule peptide components. The sample was first subjected to reduction alkylation and desalting treatment before being loaded onto the instrument. The capillary liquid chromatography column pre-column was an Acclaim PepMap RP LC C18 analysis column (5 μm) with a size of 300 μm x 5 mm, and the analysis column was an Acclaim PepMap RP LC C18 analysis column (1.9 μm) with a size of 150 μm x 150 mm. The mobile phase A was 0.1% (v / v) formic acid solution and 2% (v / v) acetonitrile solution, the mobile phase B was 0.1% (v / v) formic acid solution and 80% (v / v) acetonitrile solution, the flow rate was 600 nL / min, and the analysis time for each component was 60 min.

[0044] The MS and MS / MS parameters were as follows:

[0045] (1) MS parameters: resolution was 70000; maximum injection time was 40 ms; scan range was 300-1400 m / z.

[0046] (2) MS / MS parameters: resolution was 175000; maximum injection time was 60 ms; scan range was 300-1400 m / z;

[0047] Top N = 20; NCE / steeped NCE = 27.

[0048] The original MS / MS files were analyzed according to the sample type by Mascot software to determine the amino acid sequence of the peptide.

[0049] After searching the R4 component by mass spectrometry data, PSM FDR≤0.01 and Protein FDR≤0.01 were used as the screening criteria for peptide, site and protein identification, respectively, and 110 peptides were obtained.

[0050] Example 3 Peptide screening, synthesis and verification

[0051] 1. Prediction of the activity of polypeptides

[0052] According to the probability of peptide matching error (PEP), the peptide matching score (Score) and the peak intensity value (Intensity) of the peptide, polypeptides were screened, and those with a score and intensity of zero and a too high matching error rate were excluded. PeptideRanker was used to evaluate the possibility of biological activity of the peptide and to sort it. Among the 110 peptides, 54 peptides had a score greater than 0.5, and 12 peptides had a score greater than 0.9.

[0053] The biological activity of 74 short peptides with PeptideRanker score greater than 0.5 was evaluated by searching the BIOPEP database, and the toxicity and pi value of 54 short peptides were evaluated by Toxin Pred (toxicity prediction software). Most of the short peptides had potential or had antihypertensive (ACE inhibition, renin inhibition and release activity of vasoactive substances), hypoglycemic (DPP-IV inhibition, glucose uptake stimulating activity and alpha-glucosidase inhibitory activity), pain control (DPP-III inhibitory activity) and AChE inhibitory activity, and a small part had antioxidant activity. Through the evaluation, it was found that the 74 short peptides had no toxicity, and the pi value range was mostly 5-7, and a few was 9-11. 21 polypeptides were screened by the above conditions for molecular docking.

[0054] 2. Molecular docking

[0055] Ligand processing: The molecular structure of the polypeptide was drawn using Chem3D 19.0 software, optimized by MM2 force field, and saved as a pdb file. The pdb file was imported and hydrogenated using AutoDock software (molecular docking software), and saved as a pdbqt ligand file.

[0056] Receptor processing: The crystal structures of Fyn (2DQ7) and Keap 1 (6SP1) were downloaded from the PDB database, and the excess chloride and water molecules were removed using PyMOL software, and saved as a pdb file. The AutoDock Tools software was used to remove water and hydrogenate the receptors 2DQ7 and 6SP1, and saved as a pdbqt receptor file for standby.

[0057] Molecular docking: The vina function of AutoDock Tools software was used for molecular docking to simulate the interaction of small polypeptide molecules and macromolecular proteins. The docking center coordinates of 2DQ7 were set to (-3.031, -9.266, 39.033) (x, y, z), and the box size was 50x51x58. The docking center coordinates of 6SP1 were set to (-26.315, 20.346, -16.173) (x, y, z), and the box size was 51x51x49. The other parameters were set to default values. Then, the amino acids and polypeptide ligands were docked with the 2DQ7 crystal structure one by one.

[0058] Results: The 21 peptide segments screened above were subjected to Vina simulation docking with 2DQ7 and 6SP1, respectively. According to the Vina score, 4 small molecule peptides were screened for synthesis and verification.

[0059] Example 4 Synthesis and activity verification of small molecule peptides

[0060] 1. Synthesis

[0061] 4 small molecule peptides WTCFYE, LFLPR, WVA, FFF are synthesized by ShangHai shenguo bioengineering Co., Ltd.

[0062] 2. Activity verification

[0063] Reducing power determination: each small molecule peptide was prepared into a 20 mg / mL solution, and the in vitro reducing power of the small molecule peptide was determined according to the method in Example 1. The relevant properties and antioxidant activity verification results of each small molecule peptide are shown in Table 1.

[0064] Table 1. Relevant properties and antioxidant activity verification results of small molecule peptides

[0065]

[0066] Note: (1) The reducing power is expressed as a percentage of 0.1 mg / mL BHA; (2) Due to the randomness of molecular docking results, the Vina score shown in the table is the average of the lowest value of 9 docking results (Note: the lower the score, the better the docking result).

[0067] As can be seen from Table 1, the small molecule peptide LFLPR has strong reducing power, and the vina score and peptide segment score are high.

[0068] Example 5. Detection of the efficacy of small molecule peptides in repairing brain damage

[0069] 1. Experimental animals

[0070] Wild-type AB strain zebrafish were bred by natural pair mating. In this experiment, 4-day post-fertilization (4 dpf) zebrafish larvae were selected to evaluate the effects of specific factors on their growth and development and the expression of related genes. All zebrafish were raised in a special fish water maintained at 28°C, and the water quality conditions were as follows: 200 mg of instant sea salt was added to each 1 L of reverse osmosis water, the conductivity was 450-550 μS / cm, the pH was 6.5-8.5, and the hardness was 50-100 mg / L CaCO3.

[0071] 2. Determination of the optimal detection concentration

[0072] Four dpf wild-type AB strain zebrafish were randomly selected in a 6-well plate, and 30 zebrafish were treated in each well. Different samples were given in water, and normal control and model control groups were set up, with a volume of 3 mL per well. Except for the normal control group, the rest of the experimental groups were given aluminum chloride hexahydrate in water to establish a zebrafish brain damage model. After 48 h of treatment at 28°C, the maximum tolerated concentration (MTC) of the sample on the model zebrafish was determined, and the results are shown in Table 2 below.

[0073] Table 2. Maximum tolerated concentration of samples corresponding to each well plate

[0074]

[0075] 3. Evaluation of the inhibitory effect of neuron-specific enolase

[0076] Neuron-specific enolase (NSE) is an enzyme specific to neurons and neuroendocrine cells. As a sensitive indicator for evaluating the severity of nerve cell damage and predicting prognosis, NSE is widely used in various nerve injuries, such as cerebral hemorrhage, ischemia, hypoxia, infection, poisoning, malnutrition, etc. At the same time, NSE is also commonly used for the diagnosis and prognosis evaluation of small cell lung cancer due to its high content in neuroendocrine cells.

[0077] Under normal circumstances, serum and cerebrospinal fluid almost do not contain NSE. Recent studies have found that after the brain is damaged, some neurons necrose and disintegrate, and the integrity of the cell membrane of the brain nerve tissue is damaged, forcing NSE in the nerve cells to diffuse into the cerebrospinal fluid and intercellular space. Due to the damage to the blood-brain barrier, its integrity is damaged or permeability is enhanced, and its natural barrier function is weakened, causing some protein components to pass through the blood-brain barrier and release into the blood and cerebrospinal fluid. The content of NSE in the blood and cerebrospinal fluid after brain injury increases with the severity of brain injury, the more necrotic and disintegrated neurons, and the more severe damage to the blood-brain barrier. This mechanism provides the theoretical basis for detecting changes in NSE after brain neuron damage to evaluate the degree of nerve damage, and thus NSE is considered a specific and sensitive detection indicator for evaluating the degree of brain injury and disease prognosis.

[0078] Randomly selected wild-type AB strain zebrafish in a 6-well plate, 30 zebrafish per well. Different samples were given respectively, the positive control was donepezil hydrochloride (concentration 3.33 μg / mL), and normal control and model control groups were set up at the same time, the volume per well was 3 mL. Except for the normal control group, the rest of the experimental groups were given aluminum chloride hexahydrate to establish a zebrafish brain injury model. After 48 h of treatment at 28°C, the NSE determination kit was used, the data was collected by a multifunctional enzyme marker, and the NSE in the zebrafish was analyzed. The statistical analysis results of this indicator were used to evaluate the inhibitory effect of the sample on NSE. The statistical processing results were expressed as mean ± SE. Statistical analysis was performed using SPSS 27.0 software, where (*) indicates p<0.05, indicating that the difference is statistically significant; (**) indicates p<0.01, indicating high significance.

[0079] The results show that under the conditions of this experiment, small molecule peptide WTCFYE and small molecule peptide LFLPR have NSE inhibitory effect, and the NSE inhibitory effect of small molecule peptide WVA and small molecule peptide FFF is not obvious. The comparison of NSE fluorescence values of zebrafish after treatment with various samples is shown in Figure 1As shown in the figure, the inhibitory effect of the small molecule peptide WTCFYE is slightly lower than that of the small molecule peptide LFLPR, and the standard deviation of NSE corresponding to the small molecule peptide WTCFYE is larger, and the standard deviation of NSE corresponding to the small molecule peptide LFLPR is relatively smaller, therefore, the small molecule peptide LFLPR is preferred in the present application, and the amino acid sequence thereof is Leu-Phe-Leu-Pro-Arg, denoted as SEQ ID NO. 1, the active peptide can improve brain injury, and has a good promoting effect on the prognosis of brain injury patients.

[0080] The application can obtain further advantages and improvements without departing from the scope of the application. Although the application has been shown and described in what is considered to be the most practical and preferred embodiments, it is recognized that departures can be made therefrom within the scope and spirit of the application, which is not to be limited to the details disclosed herein, but is to be afforded the full scope of the claims so as to embrace any and all equivalents thereof. Any discussion of the prior art throughout the specification should not be viewed as an admission that such prior art is widely known or forms part of the common general knowledge in the field.

Claims

1. An active peptide for improving brain injury, characterized in that, Its amino acid sequence is shown in SEQ ID NO.

1.

2. A nucleic acid molecule, characterized in that, It encodes the active peptide of claim 1, or is reverse complementary to the nucleotide sequence encoding the active peptide of claim 1.

3. A recombinant vector, characterized in that, It contains the nucleic acid molecule of claim 2 and is capable of expressing the active peptide of claim 1.

4. A host cell, characterized in that, Its genome contains the nucleic acid molecule described in claim 2 and is able to express the active peptide described in claim 1.

5. A drug for treating brain injury-related diseases, characterized in that, It includes the active peptide as described in claim 1 and pharmaceutically acceptable excipients.

6. The drug according to claim 5, characterized in that, The excipients include one or more of the following: diluent, preservative, buffer, disintegrant, antioxidant, suspending agent, and colorant.

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