Application of STAT3 (Signal Transducer and Activator of Transcription 3) lactic acid polypeptide in preparation of product for treating colitis

Abstract

The invention belongs to the technical field of medicines, and particularly relates to application of STAT3 (Signal Transducer and Activator of Transcription 3) lactic acid polypeptide in preparation of a product for treating colitis. According to the invention, protective treatment of colitis is realized by designing STAT3 (702-714 site amino acid) lactic acid modified polypeptide, inflammatory response is alleviated by regulating and controlling an STAT3 signal channel, the lactic acid modified polypeptide can simulate the endogenous STAT3 K709 lactic acid state, and the activated STAT3 further up-regulates the expression of SOCS3 and inhibits inflammatory signal transduction; meanwhile, generation of IL-10 and other anti-inflammatory cytokines is promoted, the anti-inflammatory effect is achieved, and the colitis symptom is relieved. A new strategy is provided for clinical treatment of the inflammatory bowel disease.

Description

Technical Field

[0001] The present invention belongs to the field of medical technology, and particularly relates to an application of a STAT3 lactated polypeptide in the preparation of a product for treating colitis. Background Art

[0002] Inflammatory bowel diseases (IBD) are chronic inflammatory diseases of the colon or gastrointestinal tract, primarily including ulcerative colitis (UC) and Crohn's disease (CD). The pathogenesis remains unclear. Studies have shown that multiple factors, including susceptibility genes, the immune system, the external environment, and the intestinal microbiome, are associated with the development of the disease. The disease can be long-lasting and carries the risk of developing colon cancer, severely impacting patients' quality of life and health.

[0003] Currently, there is a lack of effective and low-toxic treatments available clinically. Existing drugs are prone to adverse reactions such as infection and drug resistance, resulting in limited efficacy. While glucocorticoids (such as prednisone) can rapidly alleviate inflammation, long-term use can lead to systemic side effects such as infection, osteoporosis, and elevated blood sugar. They are incurable and prone to relapse after discontinuation. Immunosuppressants (such as azathioprine) work by suppressing the immune system, but they can cause serious adverse reactions such as liver and kidney damage and bone marrow suppression. Their slow onset of action makes them unsuitable for patients experiencing acute exacerbations. Biologics (such as infliximab) can target inflammatory cytokines (such as TNF-α), but some patients experience primary or secondary nonresponsiveness, require regular injections, and are expensive to treat. They also carry the risk of infection (such as tuberculosis and viruses). Therefore, the development of safer and more effective treatments is urgently needed. Summary of the Invention

[0004] In order to solve the technical problems existing in the prior art, the present invention provides an application of a STAT3 lactated polypeptide in the preparation of a product for treating colitis.

[0005] To achieve the above object, the present invention adopts the following technical solutions: The first aspect of the present invention provides a polypeptide having an amino acid sequence of: YGRKKRRQRRR-AAPYLKTK LA FICVT, where K LA This indicates that the amino acid is a lactic acid-modified amino acid.

[0006] The second aspect of the present invention provides the use of the above polypeptide in the preparation of a product for treating colitis.

[0007] The third aspect of the present invention provides the use of the above polypeptide in the preparation of a product for increasing the expression level of cytokines associated with colitis.

[0008] A fourth aspect of the present invention provides a pharmaceutical composition for treating colitis, wherein the pharmaceutical composition contains the above-mentioned polypeptide as an active ingredient.

[0009] A fifth aspect of the present invention provides a pharmaceutical composition for increasing the expression level of cytokines associated with colitis, wherein the pharmaceutical composition contains the above-mentioned polypeptide as an active ingredient.

[0010] Compared with the prior art, the technical solution of the present invention has the following beneficial effects: (1) The present invention achieves protective treatment for colitis by designing a lactated modified polypeptide of STAT3 (amino acids 702 to 714), and reduces inflammatory responses by regulating the STAT3 signaling pathway. Specifically, the lactated modified polypeptide can mimic the endogenous STAT3 K709 lactated state. The activated STAT3 further upregulates the expression of SOCS3 (suppressor of cytokine signaling 3), inhibiting inflammatory signal transduction; at the same time, it promotes the production of anti-inflammatory cytokines such as IL-10 (interleukin-10), exerts anti-inflammatory effects, and alleviates colitis symptoms. The non-modified STAT3 polypeptide competes for endogenous STAT3 lactated modification, reduces the production of SOCS3 and IL-10, weakens the anti-inflammatory effect, and aggravates the colitis symptoms in mice. Animal experiments showed that tail vein injection of the lactated modified polypeptide can significantly protect the colon inflammatory state of mice, with strong targeting, high safety, and no obvious systemic adverse reactions. Tail vein injection of the non-lactated polypeptide aggravated chemically induced colitis in mice.

[0011] (2) This invention provides a strategy for the protection and treatment of colitis using lactated peptides, which improves efficacy while reducing side effects. It combines the advantages of high efficiency and low toxicity, providing a new strategy for the clinical treatment of inflammatory bowel disease. Further dose optimization and human clinical studies are planned for the future, and this approach is expected to become a new option for the treatment of IBD. BRIEF DESCRIPTION OF THE DRAWINGS

[0012] Figure 1 Schematic diagram of the design of the STAT3 polypeptide in Example 1 of the present invention, comprising a STAT3 peptide of amino acids 702-714, including a lactated peptide (Lac) at the K709 site and a non-lactated peptide (Non-Lac) at the K709 site, both of which are tagged with a transcriptional transactivator (TAT) peptide at the N-terminus to enhance the peptide's penetrating ability.

[0013] Figure 2This is the mass spectrum of the TAT-[STAT3 702-714, K709 lactate-modified] polypeptide synthesized in Example 1 of the present invention.

[0014] Figure 3 This is the mass spectrum of the TAT-[STAT3 702-714, K709 non-lactylation modified] polypeptide synthesized in Example 1 of the present invention.

[0015] Figure 4 Schematic diagram of the lactic acid modification effect of the polypeptide in Example 2 of the present invention on endogenous STAT3 in cells.

[0016] Figure 5 Schematic diagram of the activation state of STAT3 in mouse BMDM cells stimulated by LPS in Example 3 of the present invention.

[0017] Figure 6 The multi-LPS-stimulated mouse BMDM cells in Example 3 of the present invention Il10 and Socs3 Schematic diagram of mRNA expression levels.

[0018] Figure 7 Schematic diagram of the IL-10 level released by mouse BMDM cells stimulated by LPS in Example 3 of the present invention.

[0019] Figure 8 This is a schematic diagram of the weight changes of mice in the animal experiment of alleviating colitis with the polypeptide of Example 4 of the present invention.

[0020] Figure 9 This is a statistical diagram of the survival rate of mice in an animal experiment in which the polypeptide according to Example 4 of the present invention alleviates colitis.

[0021] Figure 10 This is a schematic diagram of the measurement results of mouse colon in the animal experiment of alleviating colitis with the polypeptide in Example 4 of the present invention.

[0022] Figure 11 This is a schematic diagram of the HE staining results of mouse colon in the animal experiment of alleviating colitis with the polypeptide of Example 4 of the present invention.

[0023] Figure 12 This is a schematic diagram of the results of the mouse colon histopathology scoring in the animal experiment on the polypeptide alleviating colitis in Example 4 of the present invention.

[0024] Figure 13 This is a schematic diagram of the WB results of p-STAT3 in the colon tissue of mice in the animal experiment of alleviating colitis with the polypeptide in Example 4 of the present invention. DETAILED DESCRIPTION

[0025] It should be noted that the following detailed descriptions are exemplary and intended to provide further explanation of the present invention. Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which the present invention belongs.

[0026] It should be noted that the terms used herein are only for describing specific embodiments and are not intended to limit exemplary embodiments according to the present invention. As used herein, unless the context clearly indicates otherwise, the singular form is also intended to include the plural form. In addition, it should be understood that when the terms "include" and / or "comprises" are used in this specification, they specify the presence of features, steps, operations and / or their combinations.

[0027] As introduced in the background technology, there are deficiencies in the existing treatment methods for IBD. In order to solve the above technical problems, the present invention achieves protective treatment of colitis by designing a lactated modified polypeptide of STAT3 (amino acids 702 to 714). By regulating the STAT3 signaling pathway, the inflammatory response is alleviated, the efficacy is improved and the side effects are reduced. It has the advantages of high efficiency and low toxicity, providing a new strategy for the clinical treatment of inflammatory bowel disease, and has important scientific value and clinical translation potential.

[0028] In view of this, in a typical embodiment of the present invention, a polypeptide is provided, whose amino acid sequence is YGRKKRRQRRRAAPYLKTK LA FICVT, where K LA This indicates that the amino acid is a lactic acid-modified amino acid.

[0029] like Figure 1 As shown, the present invention designed and synthesized a polypeptide containing a specific amino acid sequence of STAT3 (amino acids 702 to 714), wherein the key site K709 was lactylated and simultaneously tagged with a TAT transmembrane peptide at the N-terminus to enhance the ability of the polypeptide to enter cells. The amino acid sequence of the constructed TAT-[STAT3 702-714, K709 lactylated] is: YGRKKRRQRRR-AAPYLKTK LA FICVT.

[0030] Studies in cell-based and animal models have shown that lactated peptides can alleviate intestinal inflammation. These lactated peptides mimic the endogenous lactated state of STAT3 K709. Activated STAT3 further upregulates SOCS3 (suppressor of cytokine signaling 3) expression, inhibiting inflammatory signaling. It also promotes the production of anti-inflammatory cytokines such as IL-10 (interleukin-10), exerting anti-inflammatory effects and alleviating colitis symptoms. However, unmodified STAT3 peptides compete for endogenous STAT3 lactation, reducing SOCS3 and IL-10 production, weakening anti-inflammatory effects, and exacerbating colitis symptoms.

[0031] It should be further explained that the present invention designed a lactate-modified peptide targeting the K709 site of STAT3 (amino acids 702-714), which has a certain protective effect on colitis, indicating that lactate modification of this site has important development potential for the treatment of colitis. Subsequent research can design lactate-modified peptides at different sites on this basis for further research on the treatment of colitis.

[0032] In another embodiment of the present invention, there is provided use of the above polypeptide in preparing a product for treating colitis.

[0033] In some embodiments of the present invention, the product for treating colitis may be a drug.

[0034] In another embodiment of the present invention, there is provided use of the above polypeptide in the preparation of a product for increasing the expression level of cytokines associated with colitis.

[0035] In some embodiments of the present invention, the increasing the expression level of cytokines associated with colitis is increasing the expression level of SOCS3 and IL-10.

[0036] Specifically, the present invention stimulated mouse BMDM cells with LPS and found that cells pretreated with lactic acid modified polypeptide I110 and Socs3 At high levels, cells pretreated with non-lactated peptides significantly inhibited Il10 and Socs3 mRNA levels. Further studies have confirmed that this lactated peptide can mimic the endogenous STAT3 K709 lactation state. Activated STAT3 further upregulates SOCS3 (suppressor of cytokine signaling 3) expression, inhibiting inflammatory signaling. It also promotes the production of anti-inflammatory cytokines such as IL-10 (interleukin-10), exerting anti-inflammatory effects and alleviating colitis symptoms.

[0037] In some embodiments of the present invention, the product for increasing the expression level of cytokines associated with colitis may be a medicine.

[0038] In another embodiment of the present invention, a pharmaceutical composition for treating colitis is provided, wherein the pharmaceutical composition contains the lactic acid-modified polypeptide disclosed in the present application as an active ingredient.

[0039] In some embodiments of the present invention, the pharmaceutical composition for treating colitis further comprises a pharmaceutically acceptable carrier or excipient.

[0040] In another specific embodiment of the present invention, a pharmaceutical composition for increasing the expression level of cytokines associated with colitis is provided, wherein the pharmaceutical composition contains the lactated polypeptide disclosed in the present application as an active ingredient, and the increased expression level of cytokines associated with colitis is increased expression levels of SOCS3 and IL-10.

[0041] In some embodiments of the present invention, the pharmaceutical composition for increasing the expression level of cytokines associated with colitis further comprises a pharmaceutically acceptable carrier or excipient.

[0042] In some embodiments of the present invention, the content of the excipients in the pharmaceutical composition can be 1% by weight to 98% by weight, including but not limited to 5% by weight, 10% by weight, 20% by weight, 30% by weight, 40% by weight, 50% by weight, 60% by weight, 70% by weight, 80% by weight, 90% by weight, 95% by weight, and 98% by weight, usually accounting for about 80% by weight.

[0043] In some embodiments of the present invention, the pharmaceutical composition can be prepared in the following form: the polypeptide is mixed with a pharmaceutically acceptable carrier to obtain, for example, an oral preparation, such as tablets (including sugar-coated tablets, film-coated tablets, sublingual tablets, orally disintegrating tablets), capsules (including soft capsules, microcapsules), granules, powders, lozenges, syrups, emulsions, suspensions, films (e.g., orally disintegrating films), etc., parenteral preparations such as injections (e.g., subcutaneous injections, intravenous injections, intramuscular injections, intraperitoneal injections, instillations), external preparations (e.g., skin preparations, ointments), suppositories (e.g., rectal suppositories, vaginal suppositories), pills, nasal drops, respiratory preparations (inhalers), eye drops, etc. In addition, these preparations can be used as controlled-release preparations (e.g., sustained-release microcapsules), such as immediate-release preparations, sustained-release preparations, etc. Such preparations can be obtained by conventional preparation methods used in the art.

[0044] In some embodiments of the present invention, examples of the above-mentioned pharmaceutically acceptable carriers include excipients (e.g., starch, lactose, sucrose, calcium carbonate, calcium phosphate, etc.), binders (e.g., starch, gum arabic, carboxymethyl cellulose, hydroxypropyl cellulose, crystalline cellulose, alginic acid, gelatin, polyvinyl pyrrolidone, etc.), lubricants (e.g., magnesium stearate, calcium stearate, talc, etc.), disintegrants (e.g., carboxymethyl cellulose calcium, talc, etc.), diluents (e.g., water for injection, saline, etc.), additives (e.g., stabilizers, preservatives, colorants, flavorings, dissolution aids, emulsifiers, buffers, isotonic agents, etc.), and the like.

[0045] The drugs or pharmaceutical compositions containing the polypeptides described herein can be administered to mammals (e.g., humans, mice, rats, rabbits, dogs, cats, cattle, horses, pigs, and monkeys). Administration can be oral or parenteral (e.g., intravenous, intramuscular, subcutaneous, intra-organ, intranasal, intradermal, instillation, intracerebral, rectal, vaginal, intraperitoneal, etc.).

[0046] The dosage of the polypeptide of the present application to be administered to a subject varies depending on the administration route, symptoms, patient age, etc., and can be determined by a clinician.

[0047] The drugs or pharmaceutical compositions described in this application may also be used in conjunction with other known drugs for treating ulcerative colitis. When used together, there is no restriction on the timing of administration of each drug. Two or more different drugs may be administered simultaneously, and each drug may be administered at different times. The dosage of a known drug may be determined based on the clinically used dosage quantity and may be appropriately selected based on the intended patient, route of administration, and other factors.

[0048] In order to enable those skilled in the art to more clearly understand the technical solution of the present invention, the technical solution of the present invention will be described in detail below with reference to specific embodiments.

[0049] The sources of antibodies and reagents involved in the examples are shown in Table 1 and Table 2.

[0050] Table 1 Antibody information

[0051] Table 2 Reagent information

[0052] Example 1 Design, synthesis and determination of polypeptides like Figure 1As shown, a peptide containing a specific STAT3 amino acid sequence (amino acids 702 to 714) was designed and synthesized, in which the key site K709 was lactylated and the TAT transmembrane peptide was tagged at the N-terminus to enhance the peptide's ability to enter cells. The amino acid sequence of the constructed TAT-[STAT3 702-714, K709 lactylated] peptide is: YGRKKRRQRRR-AAPYLKTK LA FICVT. TAT-[STAT3 702-714, K709 non-lactated] peptide (YGRKKRRQRRR-AAPYLKTKFICVT) was used as a control. The above peptide was synthesized by Shanghai Chupeptide Biotechnology Co., Ltd. The mass spectrometry of TAT-[STAT3702-714, K709 lactated] peptide is as follows Figure 2 As shown, the mass spectrum of TAT-[STAT3 702-714, K709 non-lactylating modification] peptide is as follows Figure 3 shown.

[0053] In the following examples, various experiments were performed using the TAT-[STAT3 702-714, K709 lactated] and TAT-[STAT3 702-714, K709 non-lactated] peptides obtained in Example 1. The Lac group mentioned in the following experiments refers to the TAT-[STAT3 702-714, K709 lactated] peptide-treated group, and the Non-Lac group refers to the TAT-[STAT3 702-714, K709 non-lactated] peptide-treated group.

[0054] Example 2 Inhibitory effect of polypeptide on endogenous STAT3 lactylation modification Cell source and culture: (1) Bone marrow (BM) cells were obtained from 6-8 week old healthy C57BL / 6 mice and cultured in L929 cell conditioned medium for 5 days. The adherent cells at this time were mouse bone marrow-derived macrophages (BMDM). The L929 cell conditioned medium was DMEM / F-12 medium supplemented with 10% fetal bovine serum, 1% non-essential amino acids, and 1% penicillin-streptomycin, and the culture medium was collected after culturing L929 cells. (2) THP-1 cells, a human monocytic leukemia cell line, were cultured in RPMI 1640 medium containing 10% fetal bovine serum, 1% penicillin-streptomycin, and 50 mM β-mercaptoethanol. Before the experiment, the cells were induced to adhere using RPMI 1640 complete medium containing 100 nM PMA.

[0055] Treatment method: The above cells were plated into cell culture plates according to a certain ratio (6-well plate: 3.2×10 6 / well), BMDM cells required 2 hours to adhere, and THP-1 cells required 24 hours of induction of adherence using RPMI 1640 complete medium containing 100 nM PMA. The experiment began with the adhered cells. The control group cells were cultured in complete medium without synthetic peptides, while the experimental group cells were cultured in complete medium supplemented with synthetic peptides at a working concentration of 20 μM. Pretreatment was performed under these culture conditions for 24 hours, and then cell samples were collected for endogenous IP experiments.

[0056] Endogenous IP protocol: Lyse cells on ice for 30 minutes using NP40 cell lysis buffer. Centrifuge at 12,000 rpm for 10 minutes at 4°C. Collect the supernatant and transfer it to a fresh EP tube. Remove a portion of the supernatant, add SDS loading buffer, and boil the sample in a 95°C metal bath for 10 minutes. This is the input sample. Add a STAT3-specific antibody to the remaining supernatant and incubate overnight at 4°C to allow for full binding of the target protein to the antibody. Then, add Protein A / G beads and allow them to bind at room temperature for 30 minutes. Centrifuge at 500 rpm for 2 minutes at 4°C. Discard the supernatant and resuspend the beads in NP40 cell lysis buffer. Repeat this three times. Wash the beads to remove nonspecifically bound proteins. Add 1x SDS loading buffer and boil the sample in a 95°C metal bath for 10 minutes. This is the IP sample. Perform Western blotting on the prepared samples.

[0057] Western blot results are as follows Figure 4 As shown in the figure, the lactylation modification signal of endogenous STAT3 in cells pretreated with lactylated peptide was stronger, while the lactylation modification signal of endogenous STAT3 in cells pretreated with non-lactated peptide was significantly weakened.

[0058] Example 3 Effects of polypeptides on cytokine expression in BMDM cells 1. STAT3 phosphorylation WB verification experimental process and results Experimental cells: C57BL / 6 mouse BMDM cells Treatment method: BMDM cells were plated into cell culture plates according to a certain ratio (12-well plate: 1.6×10 6After BMDM cells adhered for 2 hours, they were pretreated with complete medium containing either peptide or lactated / non-lactated peptide for 24 hours. The peptide concentration was 20 μM. BMDM cells were then stimulated with LPS (100 ng / mL) for 0, 2, and 4 hours. Upon harvesting, the medium was aspirated and the cells were washed once with pre-chilled 1× PBS per well. The cells were then lysed on ice for 30 minutes using RIPA lysis buffer containing protease inhibitors. The cells were centrifuged at 12,000 rpm at 4°C for 10 minutes. The lysate was transferred to a new EP tube and the sample was boiled in SDS loading buffer at 95°C for 10 minutes in a metal bath. These samples were then used for Western blotting.

[0059] like Figure 5 As shown in the figure, after LPS stimulation of mouse BMDM cells, the activation of STAT3 in cells pretreated with lactated polypeptide was at a high level, while the phosphorylation activation of STAT3 in cells pretreated with non-lactated polypeptide was significantly inhibited.

[0060] 2. Il10 and Socs3 Expression level experimental process and results Experimental cells: C57BL / 6 mouse BMDM cells Treatment method: BMDM cells were plated into 48-well cell culture plates according to a certain ratio (0.4×10 6 BMDM cells were allowed to adhere for 2 hours. Control cells were cultured in complete medium without synthetic peptides, while experimental cells were cultured in complete medium containing lactated / non-lactated peptides at a working concentration of 20 μM. These cells were pretreated under these conditions for 24 hours. BMDM cells were then stimulated with LPS (working concentration of 100 ng / mL) for 2 hours. Trizol reagent was then added to lyse the cells, and RNA was extracted and reverse-transcribed into c'DNA for qPCR analysis to measure cytokine levels. qPCR primer sequences are shown in Table 3.

[0061] Table 3 qPCR primer sequences

[0062] like Figure 6 As shown, cells pretreated with lactated peptide showed a decrease in the number of cells after LPS stimulation. Il10 and Socs3 The expression of gene transcription level was higher in cells pretreated with non-lactated peptide after LPS stimulation. Il10 and Socs3 The expression of gene transcription level was significantly reduced.

[0063] 3. Experimental process and results of cell-released IL-10 Experimental cells: C57BL / 6 mouse BMDM cells Treatment method: BMDM cells were plated onto cell culture plates according to a certain ratio (48-well plate: 0.4×10 6 / well), after BMDM cells adhered for 2 hours, they were pretreated with complete medium without peptide or with lactated / non-lactated peptide for 24 hours, respectively. The working concentration of peptide was 20 μM. Then, LPS (working concentration was 100 ng / mL) was added to stimulate BMDM cells for 0, 4, and 8 hours. The cell culture supernatants were collected as experimental samples, and the IL-10 content in the cell culture supernatants was detected using an IL-10 ELISA kit.

[0064] like Figure 7 As shown in the figure, after LPS stimulation of mouse BMDM cells, the IL-10 released by cells pretreated with lactated peptide was at a high level, while the release of IL-10 by cells pretreated with non-lactated peptide was significantly inhibited.

[0065] Example 4 Animal Experiment on Peptide Alleviating Colitis Animal Model: 6-8 week old healthy C57BL / 6 mice were used to induce colitis with DSS. 2.5% DSS was administered in the drinking water for 5 days, after which normal drinking water was restored. The mice were divided into six groups: normal drinking water plus tail vein injection of normal saline, normal drinking water plus tail vein injection of Lac, normal drinking water plus tail vein injection of Non-Lac, DSS drinking water plus tail vein injection of normal saline, DSS drinking water plus tail vein injection of Lac, and DSS drinking water plus tail vein injection of Non-Lac. Mice were injected daily into the tail vein with a 100 μL injection volume for 13 days. The peptide dose was 10 mg / kg.

[0066] Validation criteria: Mouse survival rate and body weight were recorded daily. At the end of the experiment, mice were sacrificed, colon length was measured, and H&E staining and histopathological scoring were performed. Colon tissue was analyzed for p-STAT3 protein by Western blot. Histopathological scoring criteria are shown in Table 4.

[0067] Table 4 Histopathological scoring criteria

[0068] The mouse body weight results were as follows Figure 8 As shown in Figure 2, after 2.5% DSS was used to induce colitis in mice, tail vein injection of lactated peptide protected the mice from weight loss, while tail vein injection of non-lactated peptide reduced the weight of the mice more. Figure 9As shown in Figure 2, after 2.5% DSS was used to induce colitis in mice, tail vein injection of lactated peptide protected the survival rate of mice, while tail vein injection of non-lactated peptide significantly reduced the survival rate of mice. Figure 10 As shown in Figure 2, after 2.5% DSS was used to induce colitis in mice, tail vein injection of lactated peptide protected the mice from colon shortening, while tail vein injection of non-lactated peptide significantly shortened the mice's colon. Figure 11 As shown in Figure 2, the colon of mice injected with non-lactated peptides by tail vein showed more inflammatory cell infiltration, crypt structure destruction, and more severe colon inflammation. Figure 12 As shown in Figure 2, the colon histopathology score of mice injected with non-lactated peptides by tail vein was higher. Figure 13 As shown, the p-STAT3 in the colon tissue of mice injected with non-lactated peptide by tail vein was significantly decreased.

[0069] The above animal experiments show that tail vein injection of lactated modified peptides can significantly inhibit the aggravation of the colon inflammation state in mice, with strong targeting, high safety, and no obvious systemic adverse reactions. Tail vein injection of non-lactated peptides aggravates chemically induced colitis in mice.

[0070] Finally, it should be noted that the above is only a preferred embodiment of the present invention and is not intended to limit the present invention. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art can still modify the technical solutions described in the aforementioned embodiments or make equivalent replacements for parts thereof. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principles of the present invention should be included in the scope of protection of the present invention. Although the above describes the specific implementation methods of the present invention, it is not intended to limit the scope of protection of the present invention. Those skilled in the art should understand that, based on the technical solution of the present invention, various modifications or variations that can be made by those skilled in the art without creative work are still within the scope of protection of the present invention.

Claims

1. A polypeptide, characterized in that Its amino acid sequence is YGRKKRRQRRR-AAPYLKTK LA FICVT.

2. Use of the polypeptide according to claim 1 in preparing a product for treating colitis.

3. The use according to claim 2, characterized in that The product described is a drug.

4. Use of the polypeptide according to claim 1 in the preparation of a product for increasing the expression level of cytokines associated with colitis.

5. The use according to claim 4, characterized in that The increasing the expression level of cytokines related to colitis is increasing the expression level of SOCS3 and IL-10.

6. The use according to claim 4, characterized in that The product described is a drug.

7. A pharmaceutical composition for treating colitis, characterized in that: The pharmaceutical composition contains the polypeptide according to claim 1 as an active ingredient.

8. The pharmaceutical composition according to claim 7, wherein The pharmaceutical composition also includes a pharmaceutically acceptable carrier or excipient.

9. A pharmaceutical composition for increasing the expression level of cytokines associated with colitis, characterized in that: The pharmaceutical composition uses the polypeptide according to claim 1 as an active ingredient, and the method of increasing the expression level of cytokines related to colitis is to increase the expression level of SOCS3 and IL-10.

10. The pharmaceutical composition according to claim 9, wherein The pharmaceutical composition also includes a pharmaceutically acceptable carrier or excipient.

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