CN-121986751-A - Method for establishing anti-metabolic chemotherapeutic drug carcinogenic fatigue model

Abstract

The invention relates to the technical field of medicines, and discloses a method for establishing an anti-metabolic chemotherapeutic drug induced fatigue model, which comprises the following steps: before molding, the experimental animals are pre-given with grease solvents for 15-20 days, wherein the grease solvents comprise one or more of soybean oil, corn oil, olive oil and sesame oil, and the molding comprises the step of administering antimetabolite chemotherapeutics to the experimental animals. The model has high success rate, overcomes the defects that the prior method is easy to cause death of animals and difficult to obtain enough effective data, can effectively reflect cancer-induced fatigue caused by clinical application of antimetabolite chemotherapeutics, and is used for screening and evaluating anticancer-induced fatigue drugs.

Inventors

• LIU JUYAN
• XU WENDONG
• CAI HONGFEI
• YUAN CHENG
• CAO LIN
• MAO YUKANG
• HE YINGYING
• LI JING
• TANG SHUNZHI

Assignees

• 广州白云山汉方现代药业有限公司

Dates

Publication Date

20260508

Application Date

20241106

Claims (10)

1. 1. A method for establishing a model of anti-metabolic chemotherapeutic drug induced fatigue is characterized by comprising the step of pre-administering an oil solvent to an experimental animal for 15-20 days before modeling.
2. 2. The method of claim 1, wherein the lipid vehicle comprises one or more of soybean oil, corn oil, olive oil, sesame oil, and wherein the modeling comprises administering the antimetabolite chemotherapeutic to the subject animal.
3. 3. The method for establishing the anti-metabolic chemotherapeutic agent oncogene fatigue model according to claim 1, wherein the establishing method comprises the following steps: A. The experimental animals of the blank control group and the experimental animals of the model control group are subjected to intraperitoneal injection of sterile water, the experimental animals of the model control group, the solvent control group and the positive medicine group are subjected to intraperitoneal injection of antimetabolite chemotherapeutics for 1 time per day and 5 continuous days, the sterile water is pre-administered before the intraperitoneal injection of the experimental animals of the blank control group and the model control group, the grease solvent is pre-administered before the intraperitoneal injection of the experimental animals of the solvent control group, and the mixture of the grease solvent and the cancer fatigue positive medicine is pre-administered before the intraperitoneal injection of the experimental animals of the positive medicine group, wherein the pre-administration time is 15-20 days and 1 time per day; B. The animal fatigue level was measured by a behavioral test after 5 days of intraperitoneal injection of each group of experimental animals.
4. 4. The method for constructing a model of cancer induced fatigue of an antimetabolite chemotherapeutic agent as described in claim 3 wherein said pre-administration is gastric lavage, and wherein said pre-administration in step A is started 15-20 days before intraperitoneal injection of said laboratory animal, 1 time a day, and ends before the detection of the degree of fatigue of the animal in step B.
5. 5. The method for constructing a model of cancer causing fatigue by an antimetabolite chemotherapeutic agent as in claim 3, wherein the laboratory animals include mice, the daily dosage of intraperitoneal injection of each group of laboratory animals is 40mg/kg b.wt., the antimetabolite chemotherapeutic agent is fluorouracil, and the volume of each group of laboratory animals given in advance is 5mL/kg b.wt. each time.
6. 6. The method for building the anti-metabolic chemotherapeutic agent carcinogenic fatigue model according to claim 3, wherein the step B comprises the steps of detecting the degree of animal fatigue by adopting a behavioural experiment on the 1 st to 3 rd day after the 5 th day of intraperitoneal injection of experimental animals of each group, and the behavioural experiment comprises one or more of a rotating rod fatigue experiment and an exhaustion swimming experiment.
7. 7. The method for constructing a model of cancer induced fatigue of an antimetabolite chemotherapeutic agent as described in claim 6, wherein said method for performing said rod fatigue test comprises placing said test animal on a rod rotator, counting the time of initial drop of said test animal and the number of drops within 10 minutes from the time of placement on the rod rotator.
8. 8. The method for building the anti-metabolic chemotherapeutic agent carcinogenic fatigue model according to claim 6, wherein the method for the exhaustive swimming experiment comprises the steps of attaching a lead block with a weight of 5% to the tail of the experimental animal, putting the experimental animal into a swimming pool, counting from the beginning of water entry, and recording the exhausted swimming time by taking the condition that the head of the experimental animal cannot float out of the water surface within 5 seconds of being submerged into the water as a physical exhaustion standard.
9. 9. A model constructed according to the method for constructing a model of cancer causing fatigue of an antimetabolite chemotherapeutic agent as described in any one of claims 1 to 8.
10. 10. Use of a model according to claim 9 for studying cancer-induced fatigue caused by antimetabolite chemotherapeutics and/or evaluating the effect of a drug in treating cancer-induced fatigue.

Description

Method for establishing anti-metabolic chemotherapeutic drug carcinogenic fatigue model Technical Field The invention relates to the technical field of medicines, in particular to a method for establishing an anti-metabolic chemotherapeutic drug carcinogenic fatigue model. Background Cancer-related fatigue (CRF) is one of the most common symptoms in tumor patients and is also the most common side effect in tumor treatment. The national integrated cancer network (NCCN) defines it as "a painful, persistent, subjective, tired or tired feel related to physical, emotional, or cognitive aspects, inconsistent with recent activity, related to cancer or treatment of cancer, and impeding daily life". The international disease classification (ICD) describes the symptoms of cancer-induced fatigue as nonspecific weakness, general decline, somnolence, fatigue. It is counted that more than 75% of tumor patients can see symptoms of cancer-induced fatigue. At present, chemotherapy is still one of the main modes of tumor treatment, and common chemotherapeutic drugs include antibiotics, antimetabolites, alkaloids, alkylating agents and the like. However, while effective in killing tumor cells, chemotherapy can also bring about a number of side effects, including the development or exacerbation of cancer-induced fatigue, etc. Antimetabolite chemotherapeutics are small molecular compounds which have similar molecular structures and functions to those of metabolites in human nucleic acid synthesis and play an anticancer role by affecting nucleic acid metabolism. When the chemotherapeutics are taken by mistake in the normal metabolic process of the cells, the chemotherapeutics can inhibit key enzymes for nucleic acid synthesis or are combined with nucleic acid to insert nucleic acid molecules, abnormal codes are generated, DNA synthesis is inhibited, and cell death is finally caused. However, at present, the mechanism research of cancer induced fatigue is not exactly defined, no therapeutic drugs aiming at cancer induced fatigue are marketed, and the establishment method and the detection index of the cancer induced fatigue model of the antimetabolite drugs are still not unified standard. The applicant has adopted the method reported in the present stage of the method Ji Xiao et al in the method described in the "regulating effect of spleen-invigorating decoction on chemotherapy-related fatigue model TNF-alpha secretion" (less traditional medicine, 2019 (1): 13-15), and the method described in the Sara E.Mahoney et al in "Dietary Quercetin Reduces Chemotherapy-Induced Fatigue in Mice"(Integrative Cancer Therapies,2014,Vol.13(5):417-424) to carry out experiments, and has found that the defects still exist, such as the experiment period after injection molding is as long as 14 days, wherein the experimental animals die in the former, and the administration dosage of the latter is higher and the detection times are more. Therefore, the method solves the problems of overlong experimental period, complicated detection operation, massive death of animals and the like, establishes a representative and operable cancer-induced fatigue animal model, and has important significance for cancer-induced fatigue mechanism research and therapeutic drug screening. Disclosure of Invention The invention aims to improve a model with a long experimental period after model building aiming at a large number of death of animals in the experimental process. In order to solve the technical problems, the invention provides a method for establishing an anti-metabolic chemotherapeutic drug carcinogenic fatigue model. The model is characterized in that after a long-time grease solvent is pre-given to animals, an antimetabolite chemotherapeutic drug is injected into abdominal cavity to perform molding, the 3 rd day after molding is selected as a sampling time point, and the first falling time of a rotating rod, the falling times within 10 minutes and the exhausted swimming time are selected as detection indexes before sampling after molding. The invention adopts the following technical scheme: the establishment method of the anti-metabolism chemotherapeutic agent carcinogenic fatigue model comprises the step of pre-administering grease solvent to experimental animals for 15-20 days before modeling. As a preferred scheme of the method, the lipid solvent comprises one or more of soybean oil, corn oil, olive oil and sesame oil, and the molding comprises the step of administering an antimetabolite chemotherapeutic agent to the experimental animal. As a preferred embodiment of the method according to the invention, the establishing method comprises the following steps: A. The experimental animals of the blank control group and the experimental animals of the model control group are subjected to intraperitoneal injection of sterile water, the experimental animals of the model control group, the solvent control group and the positive medicine group are subjected to in