阅读说明：本技术 阻塞性睡眠呼吸暂停低通气综合征动物模型造模装置 (Model making device for obstructive sleep apnea hypopnea syndrome animal model ) 是由 吴昊 魏永祥 房芳 于 2018-09-11 设计创作，主要内容包括：一种阻塞性睡眠呼吸暂停低通气综合症动物模型造模装置,包括：动物造模容器、开闭机构、手套箱和麻醉装置；其中,所述动物造模容器设置在所述手套箱内,包括造模容器卡槽、头罩和气囊；所述造模容器卡槽用于实验动物的身体；所述头罩用于容纳实验动物的头部,所述头罩的一端与所述造模容器卡槽连通,另一端具有通气孔；所述气囊位于所述头罩与所述造模容器卡槽相连通的位置处,所述气囊具有供实验动物的头部穿过的通孔；所述开闭机构设置在所述手套箱内,并与所述通气孔配合,用于控制所述通气孔的开闭；所述麻醉装置用于麻醉所述实验动物。本发明操作简便,设备体积小,无需人员实时监控值守,无易燃易爆相关风险,成本低。(A device for modeling an animal model of obstructive sleep apnea hypopnea syndrome, comprising: an animal molding container, an opening and closing mechanism, a glove box and an anesthesia device; the animal molding container is arranged in the glove box and comprises a molding container clamping groove, a hood and an air bag; the molding container clamping groove is used for the body of an experimental animal; the head cover is used for accommodating the head of an experimental animal, one end of the head cover is communicated with the clamping groove of the molding container, and the other end of the head cover is provided with a vent hole; the air bag is positioned at the position where the head cover is communicated with the clamping groove of the molding container, and is provided with a through hole for the head of the experimental animal to pass through; the opening and closing mechanism is arranged in the glove box, is matched with the vent hole and is used for controlling the opening and closing of the vent hole; the anesthesia device is used for anesthetizing the experimental animal. The invention has simple operation, small equipment volume, no need of personnel to monitor on duty in real time, no associated risks of flammability and explosiveness and low cost.)

1. A device for modeling an animal model of Obstructive Sleep Apnea Hypopnea Syndrome (OSAHS), comprising: an animal molding container, an opening and closing mechanism, a glove box and an anesthesia device;

the animal molding container is arranged in the glove box and comprises a molding container clamping groove, a hood and an air bag; the molding container clamping groove is used for the body of an experimental animal; the head cover is used for accommodating the head of an experimental animal, one end of the head cover is communicated with the clamping groove of the molding container, and the other end of the head cover is provided with a vent hole; the air bag is positioned at the position where the hood is communicated with the modeling container clamping groove, the air bag is provided with a through hole for the head of the experimental animal to pass through, and when the air bag is inflated, the air bag can position the neck of the experimental animal and cut off the air circulation between the modeling container clamping groove and the hood;

the opening and closing mechanism is arranged in the glove box, is matched with the vent hole and is used for controlling the opening and closing of the vent hole;

the anesthesia device is used for anesthetizing the experimental animal.

2. An obstructive sleep apnea hypopnea syndrome animal model building apparatus as claimed in claim 1, wherein said animal modeling containers are plural in number, and a plurality of said animal modeling containers are arranged in one or more rows.

3. The modeling apparatus for an animal model with obstructive sleep apnea hypopnea syndrome according to claim 1, wherein the air bag is an annular air bag having a through hole in the middle for the head of the experimental animal to pass through.

4. The modeling apparatus of an animal model with obstructive sleep apnea hypopnea syndrome according to claim 1, wherein said balloon is connected to an air delivery device via an air tube to effect inflation and deflation of the balloon.

5. The obstructive sleep apnea hypoventilation syndrome animal model creation device as recited in claim 1, wherein said anesthesia device is an aeroanesthesia device, said anesthesia device is disposed outside said glove box and is communicated with said glove box through an air inlet and an air outlet.

6. The modeling apparatus for an animal model with obstructive sleep apnea hypopnea syndrome according to claim 1, wherein the opening and closing mechanism is an automatic piston device, and a piston of the automatic piston device is used for opening or closing the ventilation hole.

7. An obstructive sleep apnea hypopnea syndrome animal model building block as claimed in claim 1, further comprising a controller for controlling the movement of the automatic piston device.

8. An obstructive sleep apnea hypopnea syndrome animal model modeling apparatus as claimed in claim 1, wherein the number of said gloveboxes is one or more.

9. An obstructive sleep apnea hypopnea syndrome animal model modelling device as claimed in claim 1, wherein said glove box is provided with an internal environment detector, preferably selected from oxygen concentration detector, CO, internal environment detector₂One or more of a concentration detector, a temperature sensor, and a humidity sensor.

10. An obstructive sleep apnea hypopnea syndrome animal model building block as claimed in claim 1, wherein the experimental animal is a mouse, rat or rabbit.

Technical Field

The invention relates to a model building device for an experimental animal model of Obstructive Sleep Apnea Hypopnea Syndrome (OSAHS), which is particularly suitable for basic research of researching OSAHS by using animals.

Background

Obstructive Sleep Apnea Hypopnea Syndrome (OSAHS) has high incidence and great harm, and is closely related to various systemic diseases of the whole body, such as hypertension, coronary heart disease, diabetes, cerebral apoplexy and the like. Repeated hypoxia, arousal and sleep deprivation during sleep in OSAHS patients have been considered important factors in the development of physical damage, but the specific pathogenesis is still not well understood. Therefore, various animal models are continuously researched and explored to simulate the pathophysiological processes of the sleep apnea patient, such as upper airway collapse, intermittent oxygen deficiency and the like, so that the pathogenesis of the sleep apnea patient is deeply researched, and effective medicines and other treatment means are searched. The pathogenesis of the sleep disordered breathing is complex, and an animal model which can comprehensively simulate the pathophysiological process of the sleep disordered breathing is not established at present. Over the past 20 years, various types of animal models of OSAHS have been developed for one or more aspects of their pathophysiology, including experimentally induced obstructive sleep apnea animal models.

Spontaneous obstructive apnea, consistent with that of humans, cannot be fully expressed in any experimental animal. Scholars both at home and abroad have invented many experimental animal models of OSAHS to study the human obstructive sleep apnea hypopnea syndrome and its effects on cardiovascular, metabolic, psychological and other health problems. Mainly comprises an animal model manufactured by using an anoxia bin and an artificial upper airway stenosis animal model.

The animal model manufactured by using the anoxic bin simulates the characteristic of repeated intermittent anoxic and reoxygenation of the OSAHS patient in the sleeping state through the anoxic bins set by different programs so as to discuss the pathogenesis, pathophysiological process, medicine research and development and the like of the OSAHS. The molding method is most commonly used, relatively stable and reliable, and has small damage to experimental animals, and is simple and easy to implement.

It should be noted that due to the objective characteristics of the chronic intermittent hypoxia device, the studies differ in setting the frequency, minimum oxygen concentration and duration of hypoxia. These differences may lead to differences in the pathophysiological processes. An increasing number of studies on chronic intermittent hypoxia indicate that, at a given exposure time, the chronic intermittent hypoxia causes compensatory mechanisms rather than pathological changes in the body. The disadvantage of this type of model is that it can only simulate one pathophysiological characteristic of OSAHS, namely: chronic intermittent hypoxia. Therefore, the modeling study using the model is not called OSAHS animal model, but is a chronic intermittent hypoxia model. And the equipment and maintenance are expensive, and a large amount of pure oxygen, liquid nitrogen and other gases which are easy to cause danger are applied.

The sleep state oxygen supply model improved according to the hypoxia chamber model is an hypoxia chamber which carries out a preposed operation on animals, is provided with an electrode in the cranium, monitors and judges the sleep state of the animals by a computer, only gives a hypoxia environment in the sleep period and supplies oxygen with normal concentration in the arousal and waking states. Although this model is closer to the clinical OSAHS patient state, this device has some limitations on the number of single mold runs and is not suitable for long-term modeling studies.

In fact, human OSAHS is a multifactorial disease, with differences in the degree of hypoxemia and the frequency of hypoxia. Therefore, although a model of chronic intermittent hypoxia may represent part of the pathophysiological process of OSAHS, it is necessary to establish a standardized, reproducible model of chronic intermittent hypoxia.

Artificial animal models of upper airway stenosis are another major type of OSAHS modeling approach. Another important feature of OSAHS is the obstruction of upper airway collapse and the increase in negative intrathoracic pressure. Thus, intervention in pharyngeal tissues (including oropharynx and glossopharyngeal) becomes another major method and option for establishing an OSAHS model. The model comprises a modeling method for simulating upper airway collapse-reopening and a model manufactured by connecting a trachea cannula with a three-way valve. The model generally carries out upper airway catheterization or intubation operation on experimental animals, an external automatic device is connected to simulate intermittent hypoxia and intrathoracic negative pressure of OSAHS under the state of anesthesia sleep simulation, the model is close to the change of pathophysiology of OSAHS, but has certain requirements on the operation skills of experimenters, the operation has large side damage to the animals, and the model is not suitable for long-term modeling research.

The intermittent hypoxia model only represents part of pathophysiological process (chronic intermittent hypoxia) of the OSAHS, and due to the objective characteristics of chronic intermittent hypoxia equipment, the intermittent hypoxia model is different from the intermittent hypoxia model in setting hypoxia frequency, minimum oxygen concentration and duration. These differences may lead to differences in the pathophysiological processes. The use of relatively dangerous gases such as oxygen is required; the artificial upper airway stenosis animal model needs to repeatedly anaesthetize animals, cannot simulate disease states for a long time, is easy to cause side injury during operation, and needs higher technology and stability of operators. The inventor provides a model making device for an obstructive sleep apnea hypopnea syndrome mouse model, and finds that the weight of animals is easy to be reduced and suspicious intestinal tracts are damaged when the rats are subjected to intraperitoneal injection anesthesia for an ultra-long time (more than 4 weeks); the model has larger volume and occupies more space; in addition, the duration of anesthesia is limited, the general maintenance time under the dosage of sedation is about 90 minutes, and the model building time is ensured by specially-attended personnel and additional anesthetic dosage, which is relatively labor-consuming.

Disclosure of Invention

In order to solve the problems in the prior art, the invention provides a model making device for an obstructive sleep apnea hypopnea syndrome animal model, which is used for providing a good OSAHS animal model.

In order to achieve the purpose, the invention adopts the following technical scheme:

a device for modeling an animal model of obstructive sleep apnea hypopnea syndrome, comprising: an animal molding container, an opening and closing mechanism, a glove box and an anesthesia device;

the animal molding container is arranged in the glove box and comprises a molding container clamping groove, a hood and an air bag; the molding container clamping groove is used for the body of an experimental animal; the head cover is used for accommodating the head of an experimental animal, one end of the head cover is communicated with the clamping groove of the molding container, and the other end of the head cover is provided with a vent hole; the air bag is positioned at the position where the hood is communicated with the modeling container clamping groove, the air bag is provided with a through hole for the head of the experimental animal to pass through, and when the air bag is inflated, the air bag can position the neck of the experimental animal and cut off the air circulation between the modeling container clamping groove and the hood;

the opening and closing mechanism is arranged in the glove box, is matched with the vent hole and is used for controlling the opening and closing of the vent hole;

the anesthesia device is used for anesthetizing the experimental animal.

In some embodiments, the number of the animal molding containers is plural, and the plural animal molding containers are arranged in one or more rows.

In some embodiments, the air bag is an annular air bag, and the middle of the air bag is provided with a through hole for the head of the experimental animal to pass through.

In some embodiments, the balloon is in communication with an air delivery device via a vent tube to effect inflation and deflation of the balloon.

In some embodiments, the anesthesia device is a pneumoanesthesia device, and the anesthesia device is disposed outside the glove box and is in communication with the glove box through an air inlet and an air outlet.

In some embodiments, the opening and closing mechanism is an automatic piston device, and a piston of the automatic piston device is used for opening or closing the vent hole.

In some embodiments, a controller is further included for controlling the movement of the automatic piston device.

In some embodiments, the number of glove boxes is one or more.

In some embodiments, the glove box is provided with an internal environment detector.

In some embodiments, the internal environment detector is selected from the group consisting of an oxygen concentration detector, CO₂One or more of a concentration detector, a temperature sensor, and a humidity sensor.

In some embodiments, the experimental animal is a mouse, rat, or rabbit.

Compared with the prior art, the invention has the following beneficial effects:

1. the OSAHS state simulated in the invention can cover chronic intermittent hypoxia and chest negative pressure increase;

2. the invention can monitor the blood oxygen change condition of the OSAHS modeling animal at any time and reflect the effectiveness of modeling;

3. the invention has no operation side damage to the experimental animal for modeling, simulates the sleep state by qi anesthesia and has longer duration, thereby being more beneficial to the research on the chronic diseases such as OSAHS;

4. the invention can realize batch molding under different conditions in the same box body, greatly reduces the occupied space and is beneficial to the mechanism research of different subtypes of diseases;

5. the invention has simple operation, small equipment volume, no need of personnel to monitor on duty in real time, no associated risks of flammability and explosiveness and low cost.

Drawings

Fig. 1 is a schematic structural diagram of an animal model modeling apparatus according to an embodiment of the present invention;

FIG. 2 is a schematic exterior view of an animal model modeling apparatus according to an embodiment of the present invention;

FIG. 3 is a schematic view of a partial structure of an animal model modeling apparatus according to another embodiment of the present invention;

FIG. 4 is a schematic structural diagram of an animal model modeling apparatus according to another embodiment of the present invention;

FIG. 5 is a detailed view of an animal molding container and automatic piston device in accordance with an embodiment of the present invention;

FIG. 6 shows the results of the OSAHS mouse model test according to the embodiment of the present invention;

wherein, A: OSAHS mouse model blood oxygen change; b: monitoring blood oxygen change of a severe OSAHS patient in sleep; c: the OSAHS mouse model changes diaphragm myoelectricity;

FIG. 7 shows the results of the weight and blood lipid changes of two groups of mice according to the present invention;

wherein, A: body weights of two groups of mice; b: fasting serum triglycerides in both groups of mice; c: fasting serum total cholesterol in both groups of mice;

weight: body weight; TG: a triglyceride; chol: cholesterol; OSAHS: building a module; and Sham: a module is counterfeited.

Description of reference numerals:

1. a glove box; 2. a controller; 3. an air inlet; 4. an air outlet; 5. a data line; 6. an automatic piston device; 7. animal molding containers; 8. a partition plate; 9. a glove; 10. experimental animals; 11. a piston; 12. a vent hole; 13. an air bag; 14. molding a container clamping groove; 15. a head cover; 16. a one-way valve; 17. a breather pipe; 18. air anesthesia device

Detailed Description

In order that the objects, technical solutions and advantages of the present invention will become more apparent, the present invention will be further described in detail with reference to the accompanying drawings in conjunction with the following specific embodiments.

Referring to fig. 1-5, an animal model modeling apparatus for obstructive sleep apnea syndrome according to an embodiment of the present invention includes an animal modeling container 7, an opening and closing mechanism, a controller 2, a glove box 1, and an anesthesia apparatus. The opening and closing mechanism can be an automatic piston device 6, and the anesthesia device can be a anesthesia device 18. Wherein the animal modeling container 7 is used for placing an experimental animal 10 (such as a mouse, a rabbit and the like) and is connected with the automatic piston device 6, the animal modeling container 7 and the automatic piston device 6 are arranged in the glove box 1, and the automatic piston device 6 is connected with the controller 2 outside the glove box through a data line 5. The glove box 1 is communicated with the air anesthesia device 18 through an air inlet hole 3 and an air outlet hole 4.

In order to monitor the atmosphere in the glove box 1, one or more detectors, such as an oxygen concentration detector, CO, etc., may be installed₂Concentration detectors, temperature sensors, humidity sensors, and the like. Meanwhile, the animal molding container 7 may be provided with a plurality of sensors for monitoring vital signs of the laboratory animal 10, and the sensors may be connected to a data receiving device (e.g., blood oxygen detector) through a data line.

In one embodiment, the animal model molding apparatus comprises a plurality of glove boxes 1, and the anesthetic apparatus 18 may be connected to the plurality of glove boxes 1.

The number of the animal molding containers 7 may be one or more, two or more animal molding containers 7 may be arranged in a row in the glove box 1 (as shown in fig. 1), the animal molding containers 7 in a row may be connected to the same automatic piston device 6, or each animal molding container 7 may be connected to a corresponding automatic piston device 6, and a plurality of rows of animal molding containers 7 may be provided in the glove box 1 to form an array of animal molding containers (as shown in fig. 3). Rows of animal molding containers 7 may be spaced apart by partitions 8 (as shown in fig. 4).

The glove box 1 may have one or more pairs of gloves 9, depending on the number of animal moulding containers 7.

In one embodiment, the animal molding container 7 comprises a molding container slot 14, a head cover 15, and an air bag 13; wherein the molding container neck 14 is used for the body of the experimental animal 10; the head cover 15 is used for accommodating the head of the experimental animal 10, and the molding container clamping groove 14 is communicated with the head cover 15; the air bag 13 is positioned at the position where the modeling container clamping groove 14 is communicated with the head cover 15, the air bag 13 is provided with a through hole for the head of the experimental animal 10 to pass through, when the air bag 13 is inflated, the air bag 13 can position the neck of the experimental animal 10 and can cut off the air circulation between the modeling container clamping groove 14 and the head cover 15; the head cap 15 has a vent hole 12 at one end, and a piston 11 of the automatic piston device 6 is engaged with the vent hole 12 to control the opening and closing of the vent hole 12.

In one embodiment, the air bag 13 is an annular air bag with a through hole, which is fixed inside the molding container slot 14 and is located at one end of the molding container slot 14 close to the hood 15, the air bag 13 can be passed through by the animal head, and when the air bag 13 is inflated, the air bag positions the animal neck and cuts off the air circulation between the molding container slot 14 and the hood 15. The air bag 13 is connected to a vent pipe 17 through a check valve 16, and the air bag 13 is inflated by an air delivery device.

When the animal model molding device of the invention is used for animal model molding, firstly, the time cycle programs of the closed hood and the open hood of the automatic piston device are set in the cycle setting panel of the controller 2, each group of devices can respectively set different programs, and the time unit comprises: seconds, minutes, 0.1 hour, and hours. The animal molding container 7 and the automatic piston device 6 are fixed in the glove box 1 and are connected with the controller 2 outside the glove box through data lines. The experimental animal 10 is placed in a glove box 1, the glove box 1 is closed, a pneumo-anesthesia device 18 is started, the experimental animal 10 in the box is anesthetized, two hands are inserted into gloves 9 from the outside of the glove box 1, the experimental animal 10 in the box is placed in an animal molding container 7, the head of the animal is placed in a hood 15, a gas transmission device (such as an injector) is used for inflating an air bag 13 through a one-way valve 16 door, the head of the animal is clamped in the hood 15, the shape and the size of the hood 15 are matched with those of the head of the animal, and the air hole 12 only provided with the hood 15 is formed to exchange gas with the outside. The controller 2 is connected with the automatic piston device 6, and the animal can be simulated to repeatedly and discontinuously breathe according to a set circulation program by opening the switch.