CN-121987384-A - Construction method and application of canine lung space occupying lesion model

Abstract

The invention discloses a construction method and application of a canine lung space occupying lesion model. The invention provides a method for constructing a peripheral lung disease variable model at the periphery of a canine lung by injecting a temperature-sensitive hydrogel mixture through a natural cavity by utilizing a bronchoscope, which solves the technical problems of strong invasiveness, complex modeling, low success rate, uncontrollable or unstable focus images and the like in the prior art, and realizes the construction of a low-invasive, rapid, visual and stable peripheral lung disease variable canine model. Compared with the existing percutaneous puncture or open chest molding, the invention has the advantages of no need of surgical operation, high molding speed, visual imaging and strong focus stability, remarkably improves the simulation degree of an animal model on human peripheral lung lesions, and provides a high-quality experimental platform for related disease mechanism research and new technology verification.

Inventors

• ZHONG CHANGGAO
• LI SHIYUE
• JIN JING
• You Zhending
• LI HONGJIA

Assignees

• 广州医科大学附属第一医院（广州呼吸中心）

Dates

Publication Date

20260508

Application Date

20251216

Claims (10)

1. 1. A construction method of a canine lung space occupying lesion model is characterized in that under the condition of trachea cannula, an injection liquid is injected to a target position of a canine lung through the trachea cannula by using a bronchoscope and a puncture needle; The injection comprises a mixture of an Al (OH) 3 solution and a temperature-sensitive hydrogel dissolving solution, wherein the mass ratio of the Al (OH) 3 to the temperature-sensitive hydrogel is 0.01 (1-2.4); The temperature-sensitive hydrogel is a thermal shrinkage type temperature-sensitive hydrogel, is in a gel state under the temperature condition of dogs, and is compatible with Al (OH) 3 .
2. 2. The method of claim 1, wherein the temperature-sensitive hydrogel comprises a PLGA-PEG-PLGA triblock copolymer temperature-sensitive hydrogel.
3. 3. The construction method according to claim 1, wherein the injection dose of the injection is 0.13-0.17 mL/kg BW.
4. 4. The method of claim 1, wherein the injection further comprises a cell stain.
5. 5. The method of claim 4, wherein the cell stain is trypan blue.
6. 6. The construction method according to claim 4, wherein the volume ratio of the cell stain to the mixture of the Al (OH) 3 solution and the temperature-sensitive hydrogel dissolution solution is 0.1 (8-15).
7. 7. The method of claim 1, wherein the target site is located in a peripheral region of a canine lung.
8. 8. The method of claim 7, wherein the target location is at a peripheral location of the upper left lung lobe, lower left lung lobe, upper right lung lobe, and/or lower right lung lobe of the canine lung.
9. 9. The construction method according to any one of claims 1 to 8, applied to any one of the following (1) to (4): (1) Researching pathogenesis of lung placeholder lesions; (2) Study of treatment of lung placeholder lesions; (3) Preparing or screening a product for preventing and/or treating lung placeholder lesions; (4) The safety and/or efficacy of the drug is tested.
10. 10. The application of the canine lung space occupying lesion model obtained by the construction method of any one of claims 1 to 8 in any one of the following (1) to (4): (1) Researching pathogenesis of lung placeholder lesions; (2) Study of treatment of lung placeholder lesions; (3) Preparing or screening a product for preventing and/or treating lung placeholder lesions; (4) The safety and/or efficacy of the drug is tested.

Description

Construction method and application of canine lung space occupying lesion model Technical Field The invention relates to the technical field of animal experiment modeling, in particular to a method for constructing a canine lung space occupying lesion model and application thereof. Background In the field of medical research, animal models are important alternative tools for studying human diseases. Animals and humans have a certain similarity in terms of anatomy, physiology, immune system, etc., so that human disease processes can be simulated by animal models and diagnosis and treatment methods can be explored. Peripheral lung lesions are common in human respiratory diseases, such as peripheral lung tumors, inflammation, and the like. In the research of pulmonary diseases, the existing animal models are mostly limited to mice or rats, but the difference of the pulmonary structures of mice and human beings is large, the peripheral pulmonary structures of the human beings cannot be fully reflected, the body size is too small, and the requirements on operators are high. Moreover, most pulmonary molding techniques require surgical operations such as chest opening or percutaneous puncture, and anatomically define the periphery of the lung as a 3-level or beyond-3-level bronchus, and the occurrence rate of pneumothorax in clinical percutaneous puncture biopsy is as high as more than 40%, so that the method has the advantages of large damage to experimental animals, poor modeling success rate and stability and high risk of complications. In addition, the method has the problems that the visible focus with clear edges and uniform density cannot be obtained in chest CT, and the focus is difficult to maintain clear presentation for a long time in imaging, so that the human peripheral lung disease change cannot be well simulated, the requirement of researching peripheral lung disease is difficult to be met, and the related disease mechanism research and the new technology development are seriously restricted. Dogs have lung structures, respiratory physiology and immune characteristics closer to those of humans, and have larger body sizes, thus providing favorable physiological conditions for simulating human lung diseases. However, there is currently no effective, standardized canine peripheral lung disease model. Therefore, there is a need to develop a method for constructing a canine peripheral lung disease variable model that is visualized stably through natural lumen, low trauma, high success rate. Disclosure of Invention In order to solve the problems in the prior art, the invention provides a method for constructing a canine lung space occupying lesion model and application thereof. The first object of the invention is to provide a method for constructing a canine lung space-occupying lesion model. A second object of the present invention is to provide the use of the above construction method. The third object of the invention is to provide the application of the canine lung space occupying lesion model obtained by the construction method. In order to achieve the above object, the present invention is realized by the following means: The invention utilizes the bronchoscope to inject the mixture of Al (OH) 3 solution and temperature sensitive hydrogel solution through the natural cavity, builds a peripheral pulmonary disease transformation model at the periphery of the canine lung, and can be used for the foundation and transformation research of respiratory diseases, in particular peripheral pulmonary lesions. The occurrence rate of the pneumothorax through the bronchoscope biopsy is generally below 10%, and the safety of the method through the bronchoscope is obviously higher, so that the risk of animal injury caused by the method provided by the invention is greatly reduced. Medical glue belongs to strong adhesive, has larger tissue irritation and foreign body reaction, and is easy to cause local necrosis or inflammatory complications. The temperature sensitive hydrogel can flow at low temperature, is easy to inject, rapidly gels after entering a body temperature environment, forms a high-density shadow with clear edges, and can be stabilized for 2 weeks. The temperature-sensitive hydrogel molding has longer and controllable visualization in imaging, and is suitable for long-term follow-up and repeated experiments. The temperature-sensitive hydrogel and Al (OH) 3 are relatively mild immunoadjuvant and degradable materials, have low tissue irritation and inflammatory reaction, small tissue damage and few complications, are beneficial to long-term survival of animals, enable operation to be smoother, are beneficial to multipoint molding, have low technical threshold and are more suitable for popularization in common animal laboratories. A method for constructing a canine lung space-occupying lesion model comprises the steps of injecting an injection liquid to a target position of a canine lung through a bronch