CN117414363A - New use of jatrorrhizine - Google Patents
New use of jatrorrhizine Download PDFInfo
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- CN117414363A CN117414363A CN202311668216.0A CN202311668216A CN117414363A CN 117414363 A CN117414363 A CN 117414363A CN 202311668216 A CN202311668216 A CN 202311668216A CN 117414363 A CN117414363 A CN 117414363A
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- intestinal
- jatrorrhizine
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- MXTLAHSTUOXGQF-UHFFFAOYSA-O Jatrorrhizine Chemical compound COC1=CC=C2C=C3C(C=C(C(=C4)O)OC)=C4CC[N+]3=CC2=C1OC MXTLAHSTUOXGQF-UHFFFAOYSA-O 0.000 title claims abstract description 94
- 230000000968 intestinal effect Effects 0.000 claims abstract description 66
- 239000003814 drug Substances 0.000 claims abstract description 63
- 230000004083 survival effect Effects 0.000 claims abstract description 40
- 208000019155 Radiation injury Diseases 0.000 claims abstract description 27
- 230000005855 radiation Effects 0.000 claims abstract description 26
- 210000001035 gastrointestinal tract Anatomy 0.000 claims abstract description 17
- 230000000694 effects Effects 0.000 claims abstract description 16
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- 230000001681 protective effect Effects 0.000 description 4
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- PTPHDVKWAYIFRX-UHFFFAOYSA-N Palmatine Natural products C1C2=C(OC)C(OC)=CC=C2C=C2N1CCC1=C2C=C(OC)C(OC)=C1 PTPHDVKWAYIFRX-UHFFFAOYSA-N 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
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- QUCQEUCGKKTEBI-UHFFFAOYSA-N palmatine Chemical compound COC1=CC=C2C=C(C3=C(C=C(C(=C3)OC)OC)CC3)[N+]3=CC2=C1OC QUCQEUCGKKTEBI-UHFFFAOYSA-N 0.000 description 2
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- NLMDJJTUQPXZFG-UHFFFAOYSA-N 1,4,10,13-tetraoxa-7,16-diazacyclooctadecane Chemical compound C1COCCOCCNCCOCCOCCN1 NLMDJJTUQPXZFG-UHFFFAOYSA-N 0.000 description 1
- 208000006678 Abdominal Neoplasms Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- 241000037740 Coptis chinensis Species 0.000 description 1
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- YBHILYKTIRIUTE-UHFFFAOYSA-N berberine Chemical compound C1=C2CC[N+]3=CC4=C(OC)C(OC)=CC=C4C=C3C2=CC2=C1OCO2 YBHILYKTIRIUTE-UHFFFAOYSA-N 0.000 description 1
- 229940093265 berberine Drugs 0.000 description 1
- QISXPYZVZJBNDM-UHFFFAOYSA-N berberine Natural products COc1ccc2C=C3N(Cc2c1OC)C=Cc4cc5OCOc5cc34 QISXPYZVZJBNDM-UHFFFAOYSA-N 0.000 description 1
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- 238000004043 dyeing Methods 0.000 description 1
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
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- 229910052757 nitrogen Inorganic materials 0.000 description 1
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- 229920001690 polydopamine Polymers 0.000 description 1
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- 125000003039 tetrahydroisoquinolinyl group Chemical class C1(NCCC2=CC=CC=C12)* 0.000 description 1
- 238000011282 treatment Methods 0.000 description 1
- YFDSDPIBEUFTMI-UHFFFAOYSA-N tribromoethanol Chemical compound OCC(Br)(Br)Br YFDSDPIBEUFTMI-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4375—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/71—Ranunculaceae (Buttercup family), e.g. larkspur, hepatica, hydrastis, columbine or goldenseal
- A61K36/718—Coptis (goldthread)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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- Health & Medical Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Alternative & Traditional Medicine (AREA)
- Biotechnology (AREA)
- Botany (AREA)
- Medical Informatics (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention belongs to the technical field of biological medicines, and particularly discloses application of jatrorrhizine in preparation of a medicine for preventing and treating intestinal radiation injury, and a medicine for preventing and treating intestinal radiation injury. The invention verifies the effect of the jateorhizine on resisting the radiation damage of the intestinal canal by utilizing an intestinal canal organoid model, wherein the jateorhizine can obviously improve the survival rate, the budding number and the change of organoid size of the intestinal canal organoid caused by the radiation damage and eliminate the adverse effect caused by the radiation damage of the intestinal canal. Abdominal injection of jatrorrhizine after abdominal irradiation injury of experimental mice obviously increases intestinal length and survival rate, and HE staining of small intestine sections shows that crypt depth and villus structure are improved. The medicine root alkali can promote regeneration and repair of intestinal organoid after radiation, improve survival rate and improve morphological change of intestinal tract caused by radiation injury. The medicine containing jateorhizine provided by the invention can improve intestinal lesions caused by radiation injury, relieve intestinal injury symptoms and improve individual survival rate.
Description
Technical Field
The invention belongs to the technical field of biological medicines, and particularly relates to application of jatrorrhizine in preparation of a medicine for preventing and treating intestinal radiation injury, and a medicine for preventing and treating intestinal radiation injury.
Background
Radiation exposure is a public problem that jeopardizes social and human health. The gastrointestinal tract is one of the most radiation-affected organs, which is extremely vulnerable to injury and causes Acute Gastrointestinal Syndrome (AGS), or clinically known as radiation enteritis, under the action of high doses (over 10 Gy) of ionizing radiation. High doses of radiation induce loss of Intestinal Stem Cells (ISC), thereby compromising epithelial regeneration. Damaged intestinal epithelium can significantly reduce mucosal integrity, leading to electrolyte imbalance, diarrhea, weight loss, sepsis and even death. Intestinal lesions are the limiting factor in the eventual chemoradiotherapy of abdominal malignancies (such as gastric, pancreatic and colorectal cancers). Thus, radiation and/or chemotherapy at tumor killing doses often cannot be used for the treatment of abdominal tumors, resulting in low survival rates and early metastatic spread. However, currently, there is still a lack of formally approved drugs such as FDA to alleviate the radiotoxicity of the intestinal tract, so there is a need for a control measure that can be rapidly activated before or after the occurrence of a radiation event for several days.
In order to solve the above problems, chinese patent CN107669692B (second army medical science) provides a medicament for preventing and treating intestinal injury caused by ionizing radiation, wherein an active ingredient of the medicament is MPLA (glucopyranoside lipid a), and animal experiment results show that the administration of MPLA 12 hours before ionizing radiation can prolong the survival time of mice after 15gy 60co gamma-ray belly irradiation, protect intestinal villus structural integrity, promote proliferation of intestinal crypt cells and reduce apoptosis. Chinese patent CN114452283B (rocket army special medical center) provides a medicine for protecting intestinal tract from ionizing radiation injury, and the medicine effective component is polydopamine nano particles which have better protective effect on radiation enteritis induced by ionizing radiation, can inhibit apoptosis and pyrodeath of intestinal tract cells in a free radical removal mode, and protect intestinal tract stem cells from radiation injury, thereby maintaining intestinal tract steady state and function.
Jatrozine (JAT) is a tetrahydroisoquinoline alkaloid isolated from coptis chinensis, has a structure similar to berberine, and has various pharmacological functions and anti-acetylcholinesterase (AChE) activity. Research shows that jatrorrhizine has protective effect on various nervous system diseases, diabetes, arthritis and the like, and can also effectively remove ROS through autophagy as an antioxidant to protect mitochondria. In addition, jatrorrhizine can regulate intestinal flora imbalance of AD mice and improve learning and memory capacity of the mice, but the effect of jatrorrhizine on intestinal radiation injury is not reported yet.
Disclosure of Invention
The invention mainly solves the technical problem of providing a medicine for preventing and treating intestinal radiation injury and application of jatrorrhizine in preparing medicines for treating intestinal radiation injury. The invention verifies that the jateorhizine can resist intestinal radiation damage by using an intestinal organoid model, promotes regeneration and repair of the intestinal organoid after radiation, and improves the survival rate; animal experiment results show that the jateorhizine can improve the morphological change of intestinal tracts caused by radiation injury and increase individual survival rate.
In order to solve the technical problems, the invention adopts the following technical scheme:
the new application of the jatrorrhizine is as follows: application of jatrorrhizine in preparing medicines for preventing and treating intestinal radiation injury is provided. Jatrorrizine (C) 20 H 20 NO 4 ) The chemical structural formula is as follows:
as a preferred embodiment of the invention, the application is: application of jatrorrhizine in preparing medicines for relieving intestinal radiation injury is provided.
As a preferred embodiment of the invention, the applications include, but are not limited to, one or more of the following:
(1) The application of jatrorrhizine in preparing medicaments for improving the survival rate after intestinal radiation;
(2) Application of jatrorrhizine in preparing medicaments for promoting regeneration and repair after intestinal radiation;
(3) The application of jatrorrhizine in preparing medicaments for improving the survival rate of individuals after belly irradiation;
(4) Use of jatrorrhizine for the preparation of a medicament for improving intestinal length and/or morphological changes after abdominal irradiation in an individual.
As a preferred embodiment of the present invention, the intestinal morphology includes, but is not limited to, villus length, crypt depth, crypt number, etc.
A medicine for preventing and treating intestinal radiation injury comprises jatrorrhizine as medicinal component.
As a preferred embodiment of the invention, the content of the radiculine in the medicament is the medicament effect amount, and can be valued within the range of 0.01 to 99.99 weight percent according to different specifications.
As a preferred embodiment of the present invention, the medicament further comprises a pharmaceutically acceptable carrier including, but not limited to, excipients, preservatives, stabilizers, wetting agents, emulsifiers, salts for regulating osmotic pressure, buffers, and the like.
As a preferred embodiment of the invention, the dosage form of the medicament is a pharmaceutically acceptable dosage form, including but not limited to powder injection, tablet, pill, capsule, spray, dispersion and the like.
As a preferred embodiment of the present invention, the route of administration of the drug is a pharmaceutically acceptable route, including but not limited to oral, intradermal, subcutaneous, intramuscular, intraperitoneal, intravenous, and transdermal, intranasal or buccal inhalation, and the like.
As a preferred embodiment of the invention, the dosage of the medicament is a pharmaceutically acceptable dosage.
The invention has the beneficial effects that:
the invention provides a medicine for preventing and treating intestinal radiation injury, in particular to application of jatrorrhizine in preparing medicines for preventing and treating intestinal radiation injury. The invention verifies the effect of the jateorhizine on resisting the radiation damage of the intestinal canal by using an intestinal organoid model, and experimental results show that the jateorhizine can obviously improve the survival rate, bud number and organoid size change of the intestinal organoid caused by the radiation damage and eliminate the adverse effect caused by the radiation damage of the intestinal canal. Abdominal injection of jatrorrhizine after abdominal irradiation injury of experimental mice obviously increases intestinal length and survival rate, and HE staining of small intestine sections shows that crypt depth and villus structure are improved. The results show that the jateorhizine can promote regeneration and repair of intestinal organoids after radiation, and improve survival rate. The jatrorrhizine can also improve the survival rate of mice after the abdomen is irradiated, and improve the morphological change of intestinal tracts caused by radiation injury. The medicine containing jateorhizine provided by the invention can improve intestinal lesions caused by radiation injury, relieve intestinal injury symptoms and improve individual survival rate.
Drawings
FIG. 1 is a graph showing the effect of various concentrations of JAT on the growth of intestinal organoids after irradiation.
Fig. 2 is a graph showing the experimental results of the protective effect of radipine in the radioactive intestinal injury of mice in experimental examples.
The drawings in the examples and/or experimental examples are briefly described above in order to more clearly illustrate the technical solutions to be protected by the present invention. It should be understood that the above-described drawings are not to be construed as limiting the scope of the present invention in any way. Other relevant drawings may be made by those of ordinary skill in the art without undue burden from these drawings.
Detailed Description
The technical scheme of the present invention will be clearly and completely described in the following in connection with specific examples and experimental examples. It should be understood by those skilled in the art that the following examples and experimental examples are only for illustrating the technical scheme and effect of the present invention, and should not be construed as limiting the scope of the present invention. Based on the following examples, other technical solutions, such as modified, deformed or simply replaced technical solutions, obtained by a person skilled in the art without performing any inventive task, are all within the scope of the present invention.
Example 1
The embodiment provides a new application of jateorhizine, which specifically comprises the following steps: application of jatrorrhizine in preparing medicines for preventing and treating intestinal radiation injury is provided.
Example 2
The embodiment provides an application of jatrorrhizine in preparing a medicine for resisting intestinal radiation injury, which comprises one or more of the following components;
(1) The application of jatrorrhizine in preparing medicaments for improving the survival rate after intestinal radiation;
(2) Application of jatrorrhizine in preparing medicaments for promoting regeneration and repair after intestinal radiation;
(3) The application of jatrorrhizine in preparing medicaments for improving the survival rate of individuals after belly irradiation;
(4) Use of jatrorrhizine for the preparation of a medicament for improving intestinal length and/or morphological changes after abdominal irradiation in an individual.
Example 3
The embodiment provides a medicine for preventing and treating intestinal radiation injury, wherein the medicine comprises the following medicinal components in percentage by weight. Besides the effective components, the medicine also comprises a pharmaceutically acceptable oily solvent which is used for preparing the medicine into injection.
In other embodiments of the invention, the medicament may further comprise other pharmaceutically effective components (which are compounded with the jatrorrhizine to enhance the efficacy of the medicament), and pharmaceutically acceptable carriers, so as to facilitate the preparation of other pharmaceutically acceptable dosage forms.
Experimental example
1. Isolation of mouse intestinal crypts and culture of intestinal organoids
The intestinal crypt isolation and intestinal organoid culture were performed as follows:
(1) After euthanasia of the mice, 10cm small intestine was taken in an ultra clean bench, mesentery, blood vessels and fat outside the intestine were removed using elbow forceps, PBS was sucked with a 5mL syringe, and impurities inside the intestine were rinsed.
(2) The intestinal segments were cut longitudinally using sterile surgical scissors.
(3) The intestinal tracts were washed 3 times in culture dishes with pre-chilled PBS (pre-loaded with thousandth of the diabody in PBS) respectively.
(4) One end of the washed intestinal tract is clamped by elbow tweezers and is suspended on a pipe orifice of a 50mL centrifuge pipe, the intestinal tract is cut into 1cm sections by scissors from the bottom of the intestinal tract, 30mL of precooled PBS (one thousandth of double antibody is added in PBS in advance) is added, the mixture is vigorously vibrated for 90 times up and down, the supernatant is discarded, and the mixture is repeated for 5 times, so that cloudiness and foaming of the liquid can be observed.
(5) Adding 30mLPBS (one thousandth of double antibody is added in PBS) and 60 mu LEDTA, shaking up and down, embedding on ice for 30min, standing and digestion.
(6) After embedding for 30min, the mixture was poured off under shaking 30, PBS was added, and the mixture was poured off under shaking 30.
(7) 30mLPBS (one thousandth of double antibody is added in PBS) and 300 mu LEDTA are added, the mixture is shaken up and down slightly, the mixture is poured out after being placed on ice for 20min, and the mixture is rinsed for 1 time by PBS.
(8) 30mLPBS (one thousandth of the diabody was added to PBS) and 300. Mu.L of serum (final concentration of 1%) were added to the centrifuge tube, gently swirled, and vortexed for 33-40s.
(9) The mixture was filtered through a 70 μm sieve into a new 50mL centrifuge tube, designated as component 1.
(10) Repeating steps (8) - (9) for 2 times, designated as components 2, 3, respectively.
(11) Components 1, 2, 3 were centrifuged at 100g for 3min in a centrifuge at 4℃and the supernatant discarded.
(12) Depending on the amount of sediment, the sediment was resuspended in pre-chilled DMEM.
(13) mu.L of pipette tips were pre-wetted, 100. Mu.L of tips were removed therefrom and placed on a dish for bacteria, the number of crypts in 100. Mu.L of samples was counted using an inverted microscope, taking care not to count single cells or large pieces of multi-layered tissue, and the number of crypts calculated was multiplied by 10 to obtain the number of crypts per ml.
(14) Centrifuging at 4deg.C for 3min at 100g, mixing uniformly according to the ratio of culture medium to matrigel 1:1, sucking 30-50 μl of the mixed solution with a pipettor, inoculating into 96-well plate, placing into 37 deg.C incubator, adding organoid culture medium after matrigel is coagulated (usually 10 min), making it fully contact with matrigel, and making crypt capable of attaching and growing.
(15) Photographing under a microscope, counting the number of crypts, and calculating the organoid formation rate.
(16) Fresh medium was changed every 3 days.
2. Effect of different concentrations of JAT on intestinal organoid growth after irradiation
The experimental example mainly researches the influence of different concentrations of jateorhizine on the growth and development of organoids after irradiation, and comprises the following experimental steps:
(1) Crypts were randomly divided into irradiation control and JAT dosing groups of 6 wells each.
(2) Establishing an organoid irradiation model: when the crypt grows for 3 days and is in the regeneration sprouting stage, the irradiation control group and the JAT group organoids are put into an X-ray biological irradiation instrument, and the total dose is 6Gy and is 0.93Gy/min.
(3) Different concentrations of JAT (100 nM, 500nM, 1. Mu.M, 5. Mu.M, 10. Mu.M) were added to the corresponding organoids 24h after irradiation, respectively, and the control groups were treated with equal volumes of DMSO.
(4) Organoid survival was counted at day 5 after dosing, organoids budding number and average surface area were counted at day 7. The experimental results are shown in fig. 1.
Fig. 1A shows that JAT at different concentrations under a 4-fold mirror promotes regeneration of the intestinal organoids after irradiation.
FIG. 1B shows that JAT promotes survival of the intestinal organoids after irradiation, at an optimal concentration of 1. Mu.M. By counting the survival rate of the organoids on day 5, it was observed that the growth of the intestinal organoids was inhibited in the irradiation control group, and that the JAT-dosed group gradually budded and differentiated after irradiation. Irradiation control group organoid survival rate 20.5% ± 4.0%;100nM JAT group organoid survival 44.6% + -10%; 500nM JAT group organoid survival 51.3% + -8.5%; 1 mu M JAT group organoid survival rate 73.6+ -4.5%; 5. Mu.M JAT group organoid survival 59.2% + -7.7%; 10 mu M JAT organoid survival 39.7% + -1.5%.
FIG. 1C shows that JAT promotes increased budding of the intestinal organoids after irradiation, wherein the irradiation control group organoids budded 1.79.+ -. 0.10; the organoid bud number of the 100nM JAT group is 3.01+/-0.36; 500nM JAT group organoid bud count 2.57+ -0.38; 1 mu M JAT group organoid bud number 3.71+ -0.5; the organoid bud number of the 5 mu M JAT group is 3.41+/-0.25; the organoid bud number of the 10. Mu.M JAT group was 2.44.+ -. 0.77, and the result showed that 1. Mu.M JAT was the optimal treatment concentration.
FIG. 1D shows that JAT promotes an increase in the average surface area of the intestinal organoids after irradiation, the average surface area of the irradiated control group organoids (6.85.+ -. 1.1). Times.10 3 μm 2 1 mu M JAT group organoid mean surface area (10.58.+ -. 2.85). Times.10 3 μm 2 。
Comparative experiments were performed using palmatine (palmatine) having the same parent ring structure as jateorhizine and different substituents, which had the following chemical formula:
FIG. 1E shows the effect of base of BA Ma Tinggong on the survival of the intestinal organoids after irradiation at various concentrations, and FIG. 1F shows the effect of base of BA Ma Tinggong on the survival of the intestinal organoids. The results show that the base of bar Ma Tinggong has no regeneration promoting effect on the intestinal organoids after irradiation at different concentrations, which is not significantly different from the control group (P > 0.05). The active effect of jatrorrhizine is mainly determined by substituents rather than parent ring structures.
3. Protection of jatrorrhizine against radiation intestinal injury
The experimental example mainly researches and verifies the protective effect of the jatrorrhizine in the radioactive intestinal injury, and comprises the following experimental steps:
(1) Construction of C57BL/6J male mice abdomen irradiation model: 30C 57BL/6J male mice were selected, and the weight of the mice was 20-22g, and the mice were randomly divided into a WT normal group, a radiation control group and a JAT administration group, each group comprising 10 mice. The mice were anesthetized by intraperitoneal injection of 280-300. Mu.L of tribromoethanol, the limbs of the mice were fixed with paper tape, and the upper chest, upper and lower limbs and head were masked with a lead plate prepared by an X-ray bioirradiator, exposing only the abdomen of the intestinal tract 2cm 2 The mice were subjected to 14Gy abdominal irradiation using an X-ray source at a dose of 0.93Gy/min.
(2) Mice survival experiments at lethal irradiation dose: the abdomen of the mice was irradiated at 14Gy on day 0, irradiation control group: each mouse was intraperitoneally injected with 200 μl of corn oil daily for 5 consecutive days; JAT dosing group: each mouse was intraperitoneally injected with 200. Mu.L of jatrorrhizine corn oil solution (100 mg/kg JAT) at a concentration of 100mg/kg daily for 5 days. Mice survival and status were observed daily for 16 days and mice survival was calculated as follows:
mouse survival = (number of mice survived per group/total number of mice per group) x 100%.
(3) Small intestine length statistics: three mice from the WT normal group, the irradiation control group and the JAT-administered group were euthanized 5 days after administration, and small intestines were dissected, counted in length and photographed.
(4) Preparation of frozen sections of intestinal tissue: (1) 4% paraformaldehyde fixation: dissecting a mouse, obtaining a small intestine, cleaning the small intestine by precooling PBS, longitudinally cutting off the small intestine, putting the small intestine into paraformaldehyde diluted by PBS by using an acupuncture method, rolling up the small intestine by using a wood stick after 10min, putting the small intestine into a sterilized centrifuge tube, and adding 4% paraformaldehyde for overnight fixation; (2) dehydration of 30% sucrose solution: preparing 30% sucrose solution for overnight dehydration; (3) embedding small intestine tissues: placing dehydrated small intestine tissue in an embedding box, adding OCT, freezing and embedding in liquid nitrogen, and storing in a refrigerator at-20deg.C or-80deg.C; (4) the embedded small intestine tissue is placed in a frozen microtome for slicing.
(5) HE staining of small intestine tissue sections: (1) immersing the cut pieces in PBS, and washing off OCT; (2) dropwise adding hematoxylin for staining for 2min, washing with PBS for 3 times, each time for 5min, and washing residual hematoxylin staining solution; (3) dyeing with eosin staining solution for 1.5min, and washing with PBS for 3 times each for 5min; (4) treating the acidic differentiation solution for 10s, and washing the residual differentiation solution with PBS; (5) slowly sealing a slice from one side by using a cover glass to avoid bubbles as much as possible, and scanning and observing by using an intelligent pathological imaging analysis system; (6) the crypt depth and the villus length were measured. The experimental results are shown in fig. 2.
FIG. 2A is a schematic representation of 14Gy abdominal irradiation and JAT administration in mice.
FIG. 2B is a graph showing survival curves of mice in the irradiation control group and the JAT administration group. Compared with the irradiation control group, JAT can improve the survival condition of mice, and the survival rate is obviously improved.
Fig. 2C shows that JAT is able to counteract intestinal shortening due to irradiation. The length of the small intestine of the WT normal group is 32.27+/-0.65 cm, the length of the small intestine of the irradiation control group is 25.27 +/-0.9 cm, and the length of the small intestine of the JAT administration group is 30.03+/-1.95 cm.
Figure 2D shows that JAT can ameliorate damage caused by irradiation to the mouse gut. The morphological change of the small intestine is observed through HE staining, and the obvious damage of the small intestine structure after irradiation is found, which is shown by the damage of small intestine villus and the reduction of the number of crypts. Statistics of the crypt depth and the villus length of the small intestine show that the crypt and the villus length of the JAT administration group are obviously increased compared with those of a mouse of an irradiation control group, wherein the crypt depth of the irradiation control group is 46.48 +/-1.52 mu m, the villus length is 171.47 +/-4.26 mu m, the crypt depth of the JAT administration group is 85.64 +/-2.33 mu m, and the villus length is 348.56 +/-1.61 mu m.
4. Conclusion of the experiment
The invention verifies the effect of the jateorhizine on resisting the damage of the intestinal radiation by using the intestinal organoid model, and experimental results show that the jateorhizine can promote the regeneration and repair of the intestinal organoid after the radiation, and improve the survival rate. The jatrorrhizine can also improve the survival rate of mice after the abdomen is irradiated, and improve the morphological change of intestinal tracts caused by radiation injury. The medicine containing jateorhizine provided by the invention can improve intestinal lesions caused by radiation injury, relieve intestinal injury symptoms and improve individual survival rate.
Although the technical solution and effects of the present invention have been described in detail with general description, specific embodiments and experimental examples, it should be understood that modifications, substitutions or improvements may be made by those skilled in the art without departing from the spirit and scope of the present invention.
Claims (10)
1. The new application of the jateorhizine is characterized in that: the application is as follows: application of jatrorrhizine in preparing medicines for preventing and treating intestinal radiation injury is provided.
2. The new use according to claim 1, characterized in that: the application is as follows: application of jatrorrhizine in preparing medicines for relieving intestinal radiation injury is provided.
3. The new use according to claim 1, characterized in that: such applications include, but are not limited to, one or more of the following:
(1) The application of jatrorrhizine in preparing medicaments for improving the survival rate after intestinal radiation;
(2) Application of jatrorrhizine in preparing medicaments for promoting regeneration and repair after intestinal radiation;
(3) The application of jatrorrhizine in preparing medicaments for improving the survival rate of individuals after belly irradiation;
(4) Use of jatrorrhizine for the preparation of a medicament for improving intestinal length and/or morphological changes after abdominal irradiation in an individual.
4. The new use according to claim 1, characterized in that: the intestinal morphology includes, but is not limited to, villus length, crypt depth, crypt number.
5. A medicament for preventing and treating radiation damage to the intestinal tract, which is characterized in that: the medicinal components of the medicine comprise jatrorrhizine.
6. A medicament according to claim 5, characterized in that: the content of the root alkali in the medicine is the medicine effect amount, and the value is in the range of 0.01wt percent to 99.99wt percent.
7. A medicament according to claim 5, characterized in that: the medicament also includes pharmaceutically acceptable carriers including, but not limited to, excipients, preservatives, stabilizers, wetting agents, emulsifiers, salts for regulating osmotic pressure, buffers.
8. A medicament according to claim 5, characterized in that: the dosage form of the medicine is pharmaceutically acceptable, including but not limited to powder injection, tablet, pill, capsule, spray and dispersion liquid.
9. A medicament according to claim 5, characterized in that: the route of administration of the drug is a pharmaceutically acceptable route including, but not limited to, oral, intradermal, subcutaneous, intramuscular, intraperitoneal, intravenous, and transdermal, intranasal, or buccal inhalation.
10. A medicament according to claim 5, characterized in that: the dosage of the medicine is a pharmaceutically acceptable dosage.
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