CN118085038A - Polypeptide with therapeutic effect on kidney injury and application thereof - Google Patents
Polypeptide with therapeutic effect on kidney injury and application thereof Download PDFInfo
- Publication number
- CN118085038A CN118085038A CN202410283982.3A CN202410283982A CN118085038A CN 118085038 A CN118085038 A CN 118085038A CN 202410283982 A CN202410283982 A CN 202410283982A CN 118085038 A CN118085038 A CN 118085038A
- Authority
- CN
- China
- Prior art keywords
- kidney injury
- polypeptide
- ischemia reperfusion
- acute kidney
- injection
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 229920001184 polypeptide Polymers 0.000 title claims abstract description 54
- 102000004196 processed proteins & peptides Human genes 0.000 title claims abstract description 54
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 54
- 206010061481 Renal injury Diseases 0.000 title claims abstract description 23
- 208000037806 kidney injury Diseases 0.000 title claims abstract description 23
- 230000001225 therapeutic effect Effects 0.000 title claims abstract description 8
- 208000009304 Acute Kidney Injury Diseases 0.000 claims abstract description 39
- 208000033626 Renal failure acute Diseases 0.000 claims abstract description 39
- 201000011040 acute kidney failure Diseases 0.000 claims abstract description 39
- 238000002347 injection Methods 0.000 claims abstract description 27
- 239000007924 injection Substances 0.000 claims abstract description 27
- 230000010410 reperfusion Effects 0.000 claims abstract description 25
- 208000028867 ischemia Diseases 0.000 claims abstract description 24
- 125000003275 alpha amino acid group Chemical group 0.000 claims abstract description 8
- 239000003814 drug Substances 0.000 claims description 12
- 239000002504 physiological saline solution Substances 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 5
- 239000004480 active ingredient Substances 0.000 claims description 3
- 238000011282 treatment Methods 0.000 claims description 3
- 150000001413 amino acids Chemical class 0.000 claims description 2
- 108090000623 proteins and genes Proteins 0.000 claims description 2
- 239000002671 adjuvant Substances 0.000 claims 1
- 241000699670 Mus sp. Species 0.000 abstract description 13
- 101000911513 Homo sapiens Uncharacterized protein FAM215A Proteins 0.000 abstract description 4
- 102100026728 Uncharacterized protein FAM215A Human genes 0.000 abstract description 4
- 208000037978 tubular injury Diseases 0.000 abstract description 4
- 230000010024 tubular injury Effects 0.000 abstract description 4
- 238000002474 experimental method Methods 0.000 abstract description 3
- 230000000405 serological effect Effects 0.000 abstract description 3
- 241001465754 Metazoa Species 0.000 abstract description 2
- 230000006654 negative regulation of apoptotic process Effects 0.000 abstract description 2
- 238000010827 pathological analysis Methods 0.000 abstract description 2
- 210000003734 kidney Anatomy 0.000 description 5
- 206010063837 Reperfusion injury Diseases 0.000 description 4
- 238000010171 animal model Methods 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 210000003462 vein Anatomy 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 208000012947 ischemia reperfusion injury Diseases 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 108010051335 Lipocalin-2 Proteins 0.000 description 2
- 102000013519 Lipocalin-2 Human genes 0.000 description 2
- 206010063897 Renal ischaemia Diseases 0.000 description 2
- 230000006978 adaptation Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000010172 mouse model Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 102100035656 BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 Human genes 0.000 description 1
- 108090000397 Caspase 3 Proteins 0.000 description 1
- 102100029855 Caspase-3 Human genes 0.000 description 1
- 102100026550 Caspase-9 Human genes 0.000 description 1
- 108090000566 Caspase-9 Proteins 0.000 description 1
- 208000028399 Critical Illness Diseases 0.000 description 1
- 101150071461 HAVCR1 gene Proteins 0.000 description 1
- 102100034459 Hepatitis A virus cellular receptor 1 Human genes 0.000 description 1
- 101710185991 Hepatitis A virus cellular receptor 1 homolog Proteins 0.000 description 1
- 101000803294 Homo sapiens BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 Proteins 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 208000037273 Pathologic Processes Diseases 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 231100000644 Toxic injury Toxicity 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- PNNCWTXUWKENPE-UHFFFAOYSA-N [N].NC(N)=O Chemical compound [N].NC(N)=O PNNCWTXUWKENPE-UHFFFAOYSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 239000012752 auxiliary agent Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 208000020832 chronic kidney disease Diseases 0.000 description 1
- 229940109239 creatinine Drugs 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 230000000004 hemodynamic effect Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 230000021125 mitochondrion degradation Effects 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000009054 pathological process Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000012959 renal replacement therapy Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Substances C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 1
- 210000005239 tubule Anatomy 0.000 description 1
- 210000005233 tubule cell Anatomy 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention discloses a polypeptide with a therapeutic effect on kidney injury and application thereof, wherein the amino acid sequence of the polypeptide is shown as SEQ ID NO.1, and the polypeptide is applied to the kidney injury, in particular to acute kidney injury caused by ischemia reperfusion. According to animal experiments, the pathological analysis of the acute kidney injury mice induced by ischemia reperfusion by single injection of the polypeptide injection shows that large-area renal congestion and tubular injury of the acute kidney injury mice induced by ischemia reperfusion are effectively relieved, and the biochemical indexes and serological markers of the kidney injury mice induced by ischemia reperfusion by injection of the polypeptide injection are obviously reduced, and the expression inhibition of apoptosis related proteins at the kidney injury part is obvious, so that the polypeptide can be verified to effectively relieve and treat the acute kidney injury, especially the acute kidney injury induced by ischemia reperfusion.
Description
Technical Field
The invention belongs to the technical field of biopharmacology, and particularly relates to a polypeptide with a therapeutic effect on kidney injury and application thereof.
Background
Acute kidney injury is a disease with a high mortality rate worldwide, and its renal tubule cells are ischemic or suffer toxic injury causing a sharp decline in renal function. Acute kidney injury is one of the leading causes of telogenic kidney disease. Whereas ischemia reperfusion injury of the kidney is the leading cause of acute kidney injury, and has a high global mortality rate, the pathological processes of renal ischemia reperfusion include the occurrence of inflammation and the occurrence of apoptosis. Since there is currently no effective therapeutic for acute kidney injury, the primary goal of clinical intervention is to manage its cause and prognosis. The drugs used in the market are all auxiliary, for example, to manage blood sugar, blood pressure, body fluid load, cardiac output, maintain hemodynamic characteristics and oxygen supply stability, nutrient supply, etc., to reduce the severity of acute kidney injury. While critically ill patients recommend renal replacement therapy or dialysis. It is therefore highly desirable to develop drugs that alleviate the treatment of acute kidney injury, particularly renal ischemia reperfusion injury.
Disclosure of Invention
Based on the background, the invention not only provides a polypeptide with a therapeutic effect on kidney injury, but also provides application of the polypeptide.
The technical scheme of the invention is as follows:
A polypeptide with therapeutic effect on kidney injury has an amino acid sequence shown in SEQ ID NO. 1.
Based on the same inventive concept, the polypeptide is applied to the preparation of medicines for treating kidney injury.
Further, the kidney injury includes acute kidney injury.
Further, the acute kidney injury is acute kidney injury caused by ischemia reperfusion.
Further, the medicament comprises an effective amount of the polypeptide and pharmaceutically acceptable auxiliary agents.
Further, the only active ingredient in the medicament is a polypeptide.
Based on the same inventive concept, the invention also provides a polypeptide injection for treating kidney injury, which is prepared from polypeptide with an amino acid sequence shown as SEQ ID NO.1 and physiological saline.
Further, the polypeptide injection comprises an effective amount of the polypeptide.
Based on the same inventive concept, the polypeptide injection is applied to the preparation of the medicine for treating acute kidney injury caused by ischemia reperfusion.
Based on the same inventive concept, the invention also provides a gene fragment for encoding the polypeptide with the amino acid shown as SEQ ID NO. 1.
Compared with the prior art, the invention has the beneficial effects that:
according to animal experiments, the pathological analysis of the acute kidney injury mice induced by ischemia reperfusion by single injection of the polypeptide injection shows that large-area kidney congestion and tubular injury of the acute kidney injury mice induced by ischemia reperfusion are effectively relieved, and the biochemical indexes and serological markers of the kidney injury of the acute kidney injury mice induced by ischemia reperfusion by injection of the polypeptide injection are obviously reduced, and the expression inhibition of apoptosis related proteins at the kidney injury part is obvious, so that the polypeptide can be verified to effectively relieve and treat the acute kidney injury, especially the acute kidney injury induced by ischemia reperfusion, and can provide new ideas and directions for development of related medicines of the acute kidney injury and treatment of the acute kidney injury.
Drawings
FIG. 1 is a comparison of the degree of renal congestion in the sham operated and experimental groups of ischemia reperfusion-induced acute kidney injury mice animal model of example 1.
FIG. 2 is a comparison of the injury status shown by histological sections of the tubules of the sham-operated and experimental groups in an ischemia reperfusion-induced acute kidney injury mouse animal model of example 1 of the present invention.
FIG. 3 is a comparison of the changes in the levels of biochemical markers and serological markers associated with kidney injury in mice of the sham-operated and experimental groups in an ischemia reperfusion-induced acute kidney injury mouse animal model of example 1.
FIG. 4 is a comparison of the expression level change of apoptosis-related proteins at the kidney injury site of mice in the sham operation group and each experimental group in an ischemia reperfusion-induced acute kidney injury mouse animal model according to example 1 of the present invention.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention will be described in further detail with reference to the following examples thereof; it should be understood that the specific embodiments described herein are for purposes of illustration only and are not intended to limit the scope of the invention.
Example 1:
1) Preparation of polypeptide injection
The polypeptide injection of the embodiment is prepared by dissolving a polypeptide with an amino acid sequence shown as SEQ ID No.1 in physiological saline, wherein the amino acid sequence of the polypeptide is specifically shown as follows:
Tyr-Gly-Arg-Lys–Lys-Arg-Arg-Gln-Arg–Arg-Arg–Gly-Lys-Gly-Lys-Ser-Lys-Arg–Lys-Lys-Asp-Leu-Arg–Ile(YGRKKRRQRRRGKGKSKRKKDLRI).
The polypeptide used in this example was synthesized by commercial companies engaged in polypeptide synthesis, specifically, a polypeptide having a purity of 95% or more in Shanghai Jier biochemical synthesis; the physiological saline is prepared by dissolving 0.9% sodium chloride in sterile water, preparing in an ultra-clean workbench, and sterilizing at high temperature and high pressure.
The concentration of the polypeptide in the polypeptide injection in this example was 1 mg/ml.
2) Application of the polypeptide preparation in treating acute kidney injury mice induced by ischemia reperfusion
① Experimental method
The experimental mice with the same sex and the same week age are randomly divided into 4 groups, and 8 groups are respectively a sham operation group, a sham operation group for injecting the polypeptide injection, an acute kidney injury experimental group and an experimental group for injecting the polypeptide injection.
A mouse model of acute kidney injury was constructed as reported in reference (Qin S,Liu C,Chen Y,Yao M,Liao S,Xin W,Gong S,Guan X,Li Y,Xiong J,Chen J,Shen Y,Liu Y,Zhao J,Huang Y.Cobaltosic oxide-polyethylene glycol-triphenylphosphine nanoparticles ameliorate the acute-to-chronic kidney disease transition by inducing BNIP3-mediated mitophagy.Kidney Int.2023May;103(5):903-916.doi:10.1016/j.kint.2023.01.025.Epub 2023Feb 17.PMID:36805450).
An acute kidney injury experimental group and an experimental group injected with the polypeptide injection are used for preparing an acute kidney injury mouse model induced by ischemia reperfusion through operation.
A. The sham operation group is injected with physiological saline;
b. The sham operation group for injecting the polypeptide injection injects the polypeptide injection (TAT-MKK 3b, abbreviated as "pep" in each result chart) through tail vein, and the dosage is 10mg/kg body weight;
c. acute kidney injury experimental groups were subjected to vascular temporary blockage to cause ischemia reperfusion injury, and physiological saline was injected through tail vein;
d. the experimental group injected with the polypeptide injection performs temporary blocking of blood vessels to cause ischemia reperfusion injury, and TAT-MKK3b is injected through tail vein with the dosage of 10mg/kg body weight.
The dosage of each medicine is single administration dosage.
The upper mice were sacrificed within 24 hours after tail vein injection of normal saline or TAT-MKK3b and their pathology at organ, tissue and molecular level was characterized and analyzed.
② The results are shown in fig. 1 to 4, wherein fig. 1 and 2 are pathological analyses of kidney organs, wherein fig. 1 is a case of ischemia reperfusion causing large area renal congestion, fig. 2 is a case of renal tubular injury, fig. 1 and 2 are respectively apparent that ischemia reperfusion causing large area renal congestion and symptoms of renal tubular injury of a test group injected with the polypeptide injection are significantly relieved, and fig. 3 and 4 show that mice of the test group injected with the polypeptide injection are significantly reduced in serum creatinine and urea nitrogen values from ischemia reperfusion compared with those of an acute kidney injury test group, the reduction of a kidney injury marker (Kidney injury molecule 1,Kim1;Neutrophil gelatinase associated lipocalin,NGAL) is significantly reduced, and the expression of apoptosis-related proteins (CLEAVED CASPASE-3,cleaved caspase-9) at the kidney injury site thereof is significantly inhibited, corresponding to the above histological results.
The experimental results show that the polypeptide injection taking the polypeptide as the only active ingredient can obviously improve acute kidney injury induced by ischemia reperfusion in vivo, and can provide a new direction and thought for treating kidney injury, in particular acute kidney injury induced by ischemia reperfusion of kidney.
The foregoing is only a preferred embodiment of the invention, it being noted that: it will be apparent to those skilled in the art that various modifications and adaptations can be made without departing from the principles of the present invention, and such modifications and adaptations are intended to be comprehended within the scope of the invention.
Claims (10)
1. A polypeptide with therapeutic effect on kidney injury is characterized in that the amino acid sequence is shown in SEQ ID NO. 1.
2. Use of the polypeptide of claim 1 for the preparation of a medicament for the treatment of kidney injury.
3. The use of claim 2, wherein the kidney injury comprises an acute kidney injury.
4. The use according to claim 3, wherein the acute kidney injury is acute kidney injury caused by ischemia reperfusion.
5. The use according to any one of claims 2 to 4, wherein the medicament comprises an effective amount of the polypeptide, a pharmaceutically acceptable adjuvant.
6. The use according to any one of claims 2 to 5, wherein the only active ingredient in the medicament is a polypeptide having the amino acid sequence shown in SEQ ID No. 1.
7. A polypeptide injection for treating kidney injury is characterized by being prepared from polypeptide with an amino acid sequence shown as SEQ ID NO.1 and physiological saline.
8. The polypeptide injection according to claim 7, comprising an effective amount of the polypeptide.
9. The use of the polypeptide injection according to claim 7 or 8 for preparing a medicament for treating acute kidney injury caused by ischemia reperfusion.
10. A gene segment for encoding a polypeptide with an amino acid shown in SEQ ID NO. 1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202410283982.3A CN118085038A (en) | 2024-03-13 | 2024-03-13 | Polypeptide with therapeutic effect on kidney injury and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202410283982.3A CN118085038A (en) | 2024-03-13 | 2024-03-13 | Polypeptide with therapeutic effect on kidney injury and application thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN118085038A true CN118085038A (en) | 2024-05-28 |
Family
ID=91147761
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202410283982.3A Pending CN118085038A (en) | 2024-03-13 | 2024-03-13 | Polypeptide with therapeutic effect on kidney injury and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN118085038A (en) |
-
2024
- 2024-03-13 CN CN202410283982.3A patent/CN118085038A/en active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| HAUPT et al. | Effect of ibuprofen in patients with severe sepsis: a randomized, double-blind, multicenter study | |
| CN104127859B (en) | The application of polypeptide in preparation treatment or prevention medicine for treating rheumatoid arthritis | |
| JP3566283B2 (en) | Pharmaceutical composition for preventing or treating heart disease | |
| Förström et al. | Acute, generalized panniculitis with amylase and lipase in skin | |
| CN118085038A (en) | Polypeptide with therapeutic effect on kidney injury and application thereof | |
| Lo et al. | Controversies in sepsis management-what is the way forward | |
| Clark et al. | Amelioration with vessel dilator of acute tubular necrosis and renal failure established for 2 days | |
| ES2332781T3 (en) | USE OF FAB IMMUNE A DIGOXINE FOR THE REGULATION OF SODIUM / POTASSIUM ATPASA IN PRE-CLAMPTIC AND ECLAMPTIC PATIENTS. | |
| Patidar et al. | Recent advances in the management of hepatorenal syndrome: a US perspective | |
| CN114588164A (en) | Application of remazolin in prevention of perioperative hypothermia and shivering | |
| Hsu et al. | Sequential rearrangement and stereochemical reorganization to design an antimicrobial peptide with enhanced stability | |
| US3790672A (en) | Method for activating blood fibrinolysis by administration of a salt of 2-amino-ethanesulphonic acid | |
| Donati et al. | Methylene blue: An old-timer or a compound ready for revival? | |
| Sargent et al. | Octreotide‐induced hyperkalemia | |
| CN103599102B (en) | Application of Nitrosporeusines A in drugs for treating acute renal failure | |
| US20230293640A1 (en) | Compounds for the treatment of endotheliitis in context of virally caused diseases | |
| CN103599105B (en) | Application of Caesanines D in drugs used for treating acute renal failure | |
| Kim et al. | Recombinant angiotensin II therapy in a child with cardiac dysfunction and Pandoraea and Candida sepsis | |
| Graciano et al. | Carotid blow-out: A potentially fatal complication of cervical necrotizing fasciitis | |
| CN103356646B (en) | The application of Chukrasone A in preparation treatment acute renal failure medicine | |
| Giannitsis et al. | Risk stratification in patients with confirmed pulmonary embolism: what to do when echocardiography is not available | |
| CN103655538B (en) | The application of Hippolachnin A in treatment acute renal failure medicine | |
| CN114010779A (en) | Application of anti-NINJ1 antibody in preparation of medicine for treating gout and pharmaceutical preparation | |
| CN103356605B (en) | Application of Chukrasone B in preparing medicines for treating acute renal failure | |
| Johnson et al. | Tenecteplase for malignant pericardial effusion |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination |