JP2012231725A - Device and method for measuring body temperature of small animal for experiment - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a device capable of noninvasively, easily and accurately measuring a body temperature of a small animal for an experiment, and to provide a method for measuring the body temperature of the small animal for an experiment using the device.SOLUTION: The invention relates to use of a body temperature measuring system for a small animal for an experiment includes a thermostat bath capable of housing more than one animal for an experiment and a thermocamera, wherein the thermostat bath has at least a temperature and humidity control unit and a ventilation unit.

Description

  The present invention relates to an apparatus for measuring the body temperature of a small experimental animal, and a body temperature measuring method using the same.

  Animal experiments are being conducted for testing and research on the safety and effectiveness of pharmaceuticals, cosmetics, food additives, and other substances. Among various animals used in animal experiments, small laboratory animals such as mice and rats are controlled microbiologically and genetically, so the reproducibility or accuracy required for animal experiments This is important for animal experiments in that it is guaranteed to some extent.

On the other hand, body temperature is one of medically important biological indices, and it is useful to accurately measure the body temperature of experimental animals in various animal experiments.
For example, the fever observed with vaccination is regarded as a side reaction, and from the viewpoint of vaccine safety, it is desired to develop a vaccine that does not cause fever as much as possible. It is necessary to clarify in animal experiments what kind of mechanism (adjuvant) causes fever and how it affects the vaccine effect. However, because small laboratory animals such as mice and rats are usually much more nervous and timid than large animals, the body temperature of these small laboratory animals can be grasped by the hands of laboratory workers (handling). ) And fluctuate greatly depending on the ambient temperature, sound, light, etc.
Therefore, conventionally, with regard to the body temperature of small experimental animals, it has been very difficult to obtain a measurement value with excellent reproducibility by a direct body temperature measurement method performed by a laboratory worker using a temperature measurement instrument. It was.

In order to solve the above-mentioned problems, a battery-driven small temperature probe is surgically implanted in the abdominal cavity of the small animal, and after waiting for the post-operative recovery of the small animal, body temperature data under free activity is remotely transmitted. A method of obtaining (telemetry (also called telemetry)) has been developed.
According to such a remote method, it is possible to measure the body temperature without the operator approaching the small experimental animal (Non-Patent Documents 1 and 2).

However, when the present inventors examined the telemetry method as described above in detail, it was found that the following problems to be solved still exist.
(A) In order to carry out the telemetry method, it takes a lot of labor and a long preparation period, such as implanting a probe for each small experimental animal and waiting for recovery over several weeks.
(B) In order to implant a small temperature probe in the body of a small experimental animal by surgery, technical skill is required, and it is not easy to make the small experimental animal ready for testing.
(C) Since a small temperature probe is implanted in a small experimental animal by surgery, the invasion of the small animal is large.
(D) When conducting a test using a large number of small experimental animals, a great deal of labor is required for surgery and subsequent animal management.
(E) The entire measurement system is very expensive.
(F) The body temperature that can be measured is a local one around the implanted small temperature probe, and the part that can be implanted is also limited. Therefore, the body temperature change in the part away from the implanted part can be accurately determined. Difficult to measure.

GATTI et al. Am J Physiol Regulatory Integrative Comp Physiol., 282: R702-R709 (2002) Meerio et al. Physiol Behav .; 59 (4-5): 735-9 (1996)

  An object of the present invention is to provide an apparatus capable of easily and accurately measuring the body temperature of a small experimental animal with a simple and relatively inexpensive configuration, and using the apparatus, The object is to provide a method for measuring body temperature.

The present invention has the following features.
[1] a thermostatic chamber capable of accommodating one or more experimental small animals;
A thermo camera that is an imaging device part of a thermography device capable of imaging the experimental small animal and displaying the temperature of the body surface as an image,
The thermostatic chamber has at least temperature / humidity control means capable of setting the temperature and humidity suitable for survival of small laboratory animals in the tank, and ventilation means,
The thermo camera is arranged in the thermostat so that the small experimental animal can be imaged while being housed in the thermostat.
Body temperature measurement system for small laboratory animals.
[2] The body temperature measuring system according to [1], wherein the thermostatic bath further includes an illuminating means that can be controlled so as to be able to irradiate light suitable for the survival of the experimental small animal housed in the bath .
[3] The temperature and humidity control means and the illumination means of the thermostatic bath can be configured to control the temperature, humidity, and illuminance in the bath to the intended environment periodically or constantly. ] The body temperature measuring system of description.
[4] The body temperature measurement system according to any one of [1] to [3], wherein the thermostatic bath further has a soundproof structure capable of suppressing transmission of external sounds into the bath.
[5] Any one of [1] to [4], further including a main body portion of a thermography device configured to analyze data of an image captured by the thermocamera and display the data as an image showing a temperature distribution. The body temperature measurement system described.
[6] Only one thermocamera is arranged in the upper part of the thermostat bath, and the single thermocamera is configured to image all small experimental animals in the bath. The body temperature measurement system according to any one of 1] to [5].
[7] A partition for partitioning the separate regions is provided at the bottom of the thermostat bath so that a plurality of small laboratory animals can be accommodated in the thermostat bath in separate regions. The body temperature measurement system according to any one of [1] to [6] above.
[8] A storage container for storing the small experimental animal is provided at the bottom of the thermostatic chamber so as to be detachably fitted into the tank. The body temperature measurement system according to any one of the above [1] to [6], wherein the thermo camera can take an image of the experimental small animal housed in the container.
[9] A partition for partitioning the separate regions is provided in the storage container so that a plurality of small laboratory animals can be stored separately in the storage container. The body temperature measurement system according to [8] above.
[10] Using the body temperature measurement system according to any one of [1] to [9] above,
The temperature of the thermostat bath of the body temperature measurement system is set to a temperature and humidity suitable for the survival of the laboratory small animal, while the laboratory animal is kept in the bath, the laboratory animal is moved by the thermo camera of the body temperature measurement system. A method for measuring a body temperature for a small animal for experiment, which is characterized in that the temperature of the body surface of the small animal for experiment is obtained as an image based on the image data.
[11] The body temperature measurement system is the body temperature measurement system according to [3],
The body temperature measuring method according to [10] above, wherein the experimental small animal is imaged by the thermo camera while controlling the temperature, humidity, and illuminance in the tank periodically or constantly to an intended environment.

The body temperature measurement system and body temperature measurement method of the present invention not only eliminates invasion of small experimental animals related to probe implantation in the conventional telemetry method, but also a great amount of labor and cost due to probe implantation surgery and recovery, and a long time. All preparation periods can be omitted.
Moreover, in this invention, since it image | photographs, accommodating the experimental small animal in a thermostat, environment (temperature, humidity, a sound, light) can be managed so that it may become suitable for this small animal. Therefore, even a small animal such as a mouse whose body temperature tends to fluctuate due to the influence of the environment can stably record temperature changes over time.
Further, in the present invention, within the imaging range of the thermo camera, by providing a plurality of partitions in the tank, the temperature of a large number of small experimental animals placed in the same environment can be simultaneously measured by one thermo camera. Since it can be shown in the same screen, it is possible to easily compare the effects of drugs, vaccines, adjuvants, etc. on body temperature.
Furthermore, the configuration of the system is simple and relatively inexpensive compared to the configuration of the system used in the conventional telemetry method.
As described in the above description of the prior art, in the temperature measurement by the telemetry method, only the local body temperature around the probe embedded in the body is measured. Thus, not only the local body temperature but also the temperature distribution of the whole body surface of the experimental small animal can be viewed as an image, so that the administration effect of drugs, vaccines, adjuvants, etc. can be accurately followed over time. For example, by tracking the body surface maximum temperature after drug administration over time, it is possible to measure changes in body temperature as an evaluation of the whole body state similar to the measurement of trunk deep temperature by rectal temperature. Although more complicated analysis methods must be used, it is also possible to compare the temperature changes of the trunk and the extremities after drug administration, or to compare the temperature between the drug administration site and the non-administration site. Furthermore, it is also possible to evaluate the behavior and activity state of the experimental animal being observed from the thermal image itself taken over time and compare it with the measured body temperature.

FIG. 1 is a schematic diagram showing an example of the configuration of a body temperature measurement system according to the present invention. This figure is also a diagram showing a state in which the body temperature measuring method according to the present invention is carried out. In the same figure, in order to show the inside of a thermostat, the wall part is shown partially cut away. In addition, for the sake of simple illustration, the thickness of each part such as the wall and ceiling, the heat insulating structure, the temperature control structure, and the like are omitted, and the thermostat is drawn as a simple box. The same applies to FIG. 1 are assigned to the same corresponding parts in FIGS. 2 and 3 in the same manner. FIG. 2 is a schematic diagram showing another configuration example of the body temperature measurement system according to the present invention. In the figure, a net for preventing small animals from deviating from a shelf or a partition is partially drawn for easy understanding. FIG. 3 is a block diagram showing a configuration example of a body temperature measurement system according to the present invention. The line connecting the blocks in the figure is a line indicating the connection relationship between the signal wiring and the power wiring. FIG. 4 is a schematic view showing a preferred configuration example of the body temperature measurement system according to the present invention. FIG. 5 is a photographic diagram showing the temperature distribution on the body surface of the mouse, obtained in the example of the present invention. FIG. 6 is a graph showing the temperature change of the mouse body surface with time, obtained in the example of the present invention. FIG. 7 is a graph showing changes in the temperature of the body surface of the mouse accompanying changes over time after administration of LPS, obtained in the examples of the present invention.

The body temperature measuring method (the method) according to the present invention using the system will also be described below in detail while describing the configuration of the body temperature measuring system (the system) according to the present invention in detail.
In the present invention, the “constant temperature bath” means the entire apparatus configured to include at least the temperature / humidity control means and the ventilation means, and the space to be subjected to the temperature control in the constant temperature bath is simply referred to as “tank”. " Therefore, the inside of the thermostatic bath means the inside of the bath provided in the thermostatic bath.
As shown in FIG. 1, the system includes at least a thermostatic chamber 1 and a thermo camera 2. The thermostatic bath 1 has a bath configured to accommodate one or more experimental small animals (hereinafter also simply referred to as “small animals”) A. In the example of FIG. 1, the small animal A is a mouse, and the bottom surface in the tank has a size that can accommodate four mice. The thermocamera 2 is an imaging device unit included in a thermography device (the whole is not shown). Although the details of the thermography device will be described later, the thermography device is configured to include a thermo camera 2 that is an image pickup device section and a main body portion (not shown). It is an apparatus configured to be displayed as a thermal image. In the system, it is sufficient that at least the thermo camera 2 is provided in the thermostatic chamber 1.
The thermostatic chamber 1 has at least temperature and humidity control means 11 so that the inside of the bath can be controlled to a temperature and humidity suitable for the survival of the small animal A. The thermocamera 2 Is placed in the thermostat so that it can be imaged while being housed in the thermostat 1.
With the above configuration, the small animal A is kept in the thermostatic chamber 1 by the thermo camera 2 while keeping the small animal A in an environment set in accordance with the temperature and humidity suitable for the survival of the small animal A or the purpose of the experiment. The temperature of the body surface of the small animal A can be obtained as an image based on the imaged data, thereby obtaining the effects of the invention described above.

In the present invention, the small laboratory animals to be measured for body temperature include mammals, birds, reptiles, amphibians, fish, and the like. Among them, the object of the present invention is achieved to a higher degree, and the effects of the present invention are more enhanced. It is mammals that appear prominently.
When the experimental small animal is a mammal, the system specifically includes rats, mice, guinea pigs, hamsters, gerbils, rabbits, dogs, cats, minipigs, monkeys (such as marmoset, rhesus monkey, cynomolgus monkey, squirrel monkey). It can be used for body temperature measurement, and is particularly suitable for body temperature measurement of rats, mice, guinea pigs, hamsters, gerbils, or rabbits. The system is particularly suitable for measuring the temperature of sensitive rats, mice, guinea pigs, hamsters, or gerbils.

The thermostatic bath may be called an incubator, as long as it has at least temperature and humidity control means capable of controlling the temperature and humidity suitable for the survival of a small animal whose body temperature is to be measured. . The thermostat may be a modified commercial product, or may be designed and manufactured exclusively so that the system can be configured.
In addition, it is more preferable that the thermostatic bath further has a lighting means and a soundproof structure described later in order to keep the small animal in a calm state.
The temperature and humidity suitable for the survival of small animals vary somewhat depending on the type of the small animal, but in general experimental small animals, the temperature is generally in the range of 18 ° C to 35 ° C and the humidity is in the range of 30% to 80%. The selection may be made as appropriate. For example, in the case of rats and mice that are most frequently used in general animal experiments, the temperature is preferably 18 ° C. to 28 ° C., more preferably 20 ° C. to 26 ° C., and the humidity is 30% to 70%. Is preferable, and 40 to 60% is a more preferable range.
The temperature and humidity in the thermostatic bath may always be kept constant, but as will be described later, in order to reproduce the temporal change of the temperature and humidity in the bath over time, And / or periodically.

In the example of FIG. 1, an exhaust pipe 11 a for discharging air in the tank and an air supply pipe 11 b for introducing air having appropriate temperature and humidity into the tank are drawn. The control means 11 is suggested. A heat exchange mechanism, a control system, etc., which are the main body of the temperature and humidity control means, are not shown.
In the example of FIG. 3, the temperature / humidity control means 11 is drawn independently from the outside of the tank, but the tank and the temperature / humidity control means may be provided in a single casing. Further, as shown in FIG. 3, the temperature / humidity control means may receive a command from an external control device 3 separate from the thermostatic bath and operate to control the temperature in the bath.

The thermostat bath may be any tank that can accommodate one or more small animals in the bath, but the cost of equipment per small animal is reduced, the space occupied by the equipment is smaller, and the same In view of the usefulness of experiments in which the body temperature is measured simultaneously in the environment, it is preferable to allow a plurality of small animals to be accommodated.
The storage of the small animals in the thermostat is not described in the forced posture of the small animals, and the original posture of the small animals, preferably in a state where a space is provided so that an appropriate operation is possible. It is preferable to accommodate such that it can be imaged by a thermo camera.

In the thermostatic bath, the positional relationship between the small animal and a thermo camera described later is important, and it is a preferable aspect that the small animal is arranged on a plane perpendicular to the imaging optical axis of the thermo camera.
In the example of FIG. 1, the small animal A is arrange | positioned on the bottom face in the tank of a thermostat, and it has the structure imaged with the thermo camera 2 arrange | positioned on the ceiling. Moreover, in the example of FIG. 2, the shelf is provided in the side surface, the small animal A is arrange | positioned, and it is set as the structure imaged with the thermo camera 2 arrange | positioned on the opposite side surface.
The embodiment shown in FIG. 2 is characterized in that a small animal can be imaged from the side. However, since the small animal A needs to be covered with a net or the like so as not to deviate from the shelf or partition, the number of parts increases and the net is increased. This is an obstacle to imaging. On the other hand, the configuration in which an animal is arranged on the bottom surface in the tank and is imaged by the thermo camera 2 arranged above (particularly the ceiling) as shown in the embodiment of FIG. 1 needs to be covered with a net or the like. This is a preferable mode because a small animal can be directly viewed with a thermo camera.

As shown in FIG. 1, in a mode in which a plurality of small animals are arranged on the bottom surface in the tank, an inter-individual that can occur when a small animal does not become an obstacle to imaging of other small animals and when a small animal is raised in a group. In order to prevent fighting or the like in the tank, a mode in which a partition 12 for partitioning the region is provided at the bottom of the tank and small animals are accommodated in separate regions is preferable. However, it does not exclude the breeding of a plurality of animals in one section depending on the purpose of the experiment.
The form of the partition is not particularly limited. However, since the bottom shape of a general tank is rectangular, a grid-like partition as shown in FIG.
When a partition is provided on the bottom surface in the tank, the size of the floor area to be given to each small animal may be appropriately determined according to the type of the small animal. In this case, the size of the floor area per animal is not only the area value but also the shape of the floor area. For example, in the case of a rectangular floor region, a rectangle composed of a short short side and a long long side where the small animal cannot move is not preferable from the viewpoint of keeping the small animal calm even if the area is large. However, this is not necessarily the case depending on the request for the experiment.
Moreover, even if an excessively wide area is given to each small animal, the cost effectiveness and measurement efficiency are lowered, and it is useless because it does not particularly contribute to the rest of the small animal.
In addition, the floor area to be given to each small animal and the outer peripheral shape of the entire bottom face in the tank in which they are added are the shape of the imaging area of the thermo camera itself (for example, if it is a pixel of 640 × 480, the aspect ratio 4: 3) is preferable because it does not cause a useless area on the imaging screen.
In consideration of the above points, for example, in the case of a mouse having a head torso length of 50 mm to 70 mm (weight 17 to 23 g) excluding the tail, the shape of the floor region to be given to one mouse is 80 mm long × 140 mm wide. It is a rectangle (vertical quadrilateral) of about 140 mm in length and 300 mm in width, and a rectangle in which about 80 mm in length x 140 mm in width to about 100 mm in length and 160 mm in width is a more preferable shape.
In addition, in the case of a rat having a head torso length of 200 mm to 350 mm (body weight 200 to 500 g) excluding the tail, the shape of the floor area to be given to one animal is about 150 mm x 300 mm x 350 mm x 420 mm. It is a rectangle (right-angled quadrilateral), and a rectangle with a length of about 200 mm × width 350 mm to length 300 mm × width 400 mm is a more preferable shape.
In the case of a rabbit having a body weight of 2 to 5 kg, the shape of the floor area to be given to one animal is a rectangle (vertical quadrilateral) of about 350 mm long × 400 mm wide to 500 mm long × 900 mm wide. A rectangle having a width of about 600 mm to a length of about 550 mm × width of about 650 mm is a more preferable shape.
The shape of the floor area for other small experimental animals (such as squirrel monkeys and cynomolgus monkeys) is selected as appropriate so that each small animal can be bred calmly according to their body shape, habits, stress resistance, experimental purpose, etc. do it.

Considering the shape of the bottom of the bottom of a general thermostatic bath 320 mm × width 610 mm to length 550 mm × width 640 mm and the shape of the above individual floor areas, the individual floor areas divided by the grid-like partitions For example, 1 × 1 to 2 × 3 for rats, 2 × 2 to 4 × 6 for mice, and 1 × 1 to 1 × 2 for rabbits are preferable.
The shape of the floor area, the shape of the bottom surface in the tank, and the arrangement pattern of the floor area are just preferable examples. Depending on the content and purpose of the test, two or more small animals are arranged in one floor area. Alternatively, a particularly large thermostatic bath may be designed and manufactured to exceed the shape of the floor region, the shape of the bottom surface in the bath, and the arrangement pattern of the floor region.

In the example of FIG. 1, the partition 12 is drawn directly in the bath of the thermostat 1, but it is easier to actually arrange, breed, and take out small animals, and to clean and maintain the thermostat. From this point, as shown in FIG. 4, it is preferable that a container 14 for accommodating the small animal is separately prepared and detachably fitted into the tank. A small animal housed in the housing container is imaged by the thermo camera 2.
When accommodating a plurality of small animals, a partition 15 similar to that shown in FIG. 1 may be provided in the accommodating container as necessary.

As shown in FIG. 3, the thermostat is preferably provided with an illuminating means 13 that can be controlled so that light suitable for the survival of small animals in the bath can be irradiated.
The light suitable for the survival of the small animal is at least an intensity that gives an illuminance such that the small animal can be at rest. The light may be white light including wavelength components of the three primary colors of light, but only specific wavelength components may be selected according to the purpose of the experiment.
The illuminance preferred by small animals varies depending on the type of small animal. For example, in mice, rats or rabbits, 150 to 300 lux at a height of 80 mm from the floor, or 200 lux at a height of 1000 mm is preferable. It is not limited to the range.
What is necessary is just to select suitably the illumination means for irradiating the said light in a tank, such as introduction of external light by a fluorescent lamp, an incandescent lamp, LED, and an optical fiber.

By using the temperature and humidity control means and the illumination means to control the temperature, humidity, and illuminance in the tank periodically or constantly to the intended environment, the sleep-wake cycle of a small animal in the tank, Hormonal secretion cycle, autonomic nervous function, motor activity, etc. are kept in a controlled experimental environment that is strictly controlled without being affected by the season or installation location. The intended environment in the present invention means that, for example, when a temporal change in temperature, humidity and illuminance of the day is simulated in the tank, the lighting is completely over the day for the purpose of examining the correlation between sunshine and motor activity. The case where it does not attach is mentioned. The ratio of light period: dark period = 14: 10 or 12:12 is preferable as the light-dark period when the temporal change in temperature, humidity, and illuminance of the day is simulated in the tank.
It is possible to accurately measure changes in body temperature due to administration of drugs, vaccines, adjuvants, etc. by imaging with a thermo camera while keeping the small animal in such a state.

  It is preferable to provide the thermostatic chamber with a soundproof structure that can suppress the transmission of external sounds, and keep the interior of the chamber more quiet. As a temporary measure for controlling the noise level, it is preferably 60 dB (A) or less in the thermostatic chamber (in the absence of animals). This makes it possible to remove the alertness and stress of mice and rats that are particularly sensitive to sound, so that they are affected by the sound of daily life and general mechanical sounds in experimental facilities. And can contribute to accurate measurement of body temperature change.

  Exhaust hair, dandruff, urine (spray), food powder, suspended particles such as microorganisms, odor of manure (ammonia, hydrogen sulfide, trimethylamine, methyl mercaptan, etc.), carbon dioxide, etc. The ventilation means 11 for taking in fresh outside air needs to be provided. Thereby, the air in a tank can be kept clean and the stress of the experimental small animal can be reduced. However, if the number of ventilations increases too much, it can be a hindrance to keep the temperature inside the thermostat bath constant, and if the airflow speed around the animal increases, the wind will be strongly applied to the skin of the experimental animal, which will cause stress. Therefore, the number of ventilations is preferably about 10 to 15 times / hour (about 8 to 15 times / hour in the case of the unidirectional airflow method). For the purpose of improving ventilation efficiency, it is also effective to attach a deodorizing filter to the exhaust port and / or to use a bedding that is excellent in ammonia adsorption and hardly generates dust.

The thermography apparatus may be any device that can capture an image of a small animal, which is an object, with a thermocamera, which is an imaging portion, process the captured image data, and represent the surface temperature difference of the small animal as an image. A typical thermography device detects infrared radiant energy emitted from an object, and changes the density or color of the image according to the amount of infrared radiant energy, thereby visualizing the temperature distribution and image (thermal And a device that displays the image as an image).
In this system, as shown in FIG. 1, at least the thermo camera may be provided in the thermostatic bath.
In order to make the imaging data obtained by the thermo camera into an image showing the temperature distribution, the main part of the thermography device (a processing device including a computer configured to process the imaging data and output a thermal image) or an image A display device (display, printer, etc.) is required, but these may be included in the system as an auxiliary device, or may be an external device separately prepared by the user.
The main part of the thermocamera and the thermography device does not necessarily have to be separated from each other, and may be a compact photographic display device in which both are integrated, and further a data signal from there to another processing device. It is good also as a structure to take out.
As long as the thermocamera is for thermography, it may be a camera capable of capturing moving images, a camera dedicated to still images, or a complex machine of both.
[The thermocamera is placed in the thermostat so that it can take images of small experimental animals while being housed in the thermostat] means that the entire thermocamera is contained in the thermostat. 1, it is meant to include a mode in which at least the imaging lens portion of the camera is exposed in the thermostatic chamber so that a small animal can be imaged. In addition, with the arrangement of the thermo camera, heat insulation measures and a protective case for the camera may be provided as appropriate.

A plurality of thermocameras may be arranged in the tank. However, as illustrated in FIG. 5, the mode in which all the small animals in the tank are imaged with one thermocamera is economical and economical. This is a preferable aspect in terms of both processing and comparison.
1 to 3, each small animal A divided and accommodated by the partition 12 is captured by one thermocamera 2 so as to fit in one image.

FIG. 3 is a block diagram showing a configuration example of the system.
In the example of the figure, the entire thermography apparatus is included in the system. The thermo camera 2 is connected to a main body portion (computer) 3, and data of an image captured by the thermo camera 2 is analyzed in the main body portion 3 and displayed on the image display device 4 as an image showing a temperature distribution. It has a configuration.
The image display device may be a printer or the like in addition to a liquid crystal display or a CRT display, but the color of the image is easier to understand than black and white.

In the system configuration example of FIG. 3, the computer that is the main body part 3 of the thermographic apparatus not only performs image data processing inherent to the thermographic apparatus, but also controls the illumination means 13 and the temperature / humidity control means 11. It is a central control device that reproduces the illuminance in the intended tank environment.
In the system configuration example of FIG. 3, separate devices are connected to each other. However, these devices may be integrated into one housing.

  The use of the system is not particularly limited as long as it is a use for measuring body temperature, which is one of physiological indices, in animal experiments using small experimental animals. Specific examples of applications include, for example, measurement of changes in body temperature associated with administration of drugs, vaccines, adjuvants, etc. to small experimental animals, and behavioral physiology, body temperature as an index for investigating the sleep cycle of small experimental animals. Measurement and the like. The system is also applicable to highly sensitive small animals, so a fever test using rabbits (http://dmd.nihs.go.jp), which is currently essential when applying for new drugs, etc. /iso-tc194/pyrogenicity.htm) can also be used for replacement with mice. In recent years, studies have been made to replace the rabbit fever test (in vivo) with an in vitro test system such as endotoxin test (http://jacvam.jp/files/news/pyrogen_20100216.pdf). The system will continue to be necessary, and it is worthwhile to replace rabbits with mice that are smaller and easier to control.

When the hair of a small experimental animal interferes with the measurement of the body surface skin temperature, the skin body surface temperature at that site can be measured by appropriately shaving the target site.
In the case of at least a mouse, if the temperature in the tank is set low, there is a high possibility that heat dissipation from the body surface will exceed heat generation. Therefore, for example, as shown in the following examples, in order to measure the increase in body temperature caused by administration of lipopolysaccharide (LPS) with the system of the present invention, it was necessary to set the temperature in the tank to about 30 ° C. .
When using this system, it is important to set an appropriate environmental temperature according to the type and size of the animal used and according to the purpose of the experiment.

Example 1
In this example, the system shown in FIG. 1 was constructed as the system, LPS was actually administered to the mouse, the mouse was placed in the thermostat of the system, and the body temperature change of the mouse was measured.
Experimental method :
The thermostat is Sanyo MIR-254 (700 mm x 580 mm x 1618 mm; outer dimensions, 600 mm x 320 mm x 1100 mm; inner dimensions), and the thermocamera is FLIR b60 (resolution 180 x 180 pixels, temperature, manufactured by FLIR SYSTEMS). The heat measurement system was composed of a laptop computer for data processing with a resolution of 0.08 ° C. A container of 320 mm × 210 mm × 300 mm was prepared in this tank and divided into four sections by a partition. One mouse was placed in each of the four compartments. The floor area per mouse is 85mm x 100mm. Food and water were freely available.
The camera was installed at a height of 810 mm from the bottom so that it could capture images perpendicular to the bottom. The bath temperature was set to 30 ° C., and the lighting was turned on from 6 am to 6 pm (light / dark cycle was 12:12).
The mouse was anesthetized and the hair on the back was shaved with an electric clipper, and then acclimated and raised in the above environment for 2 to 3 days. Two animals were the LPS group, the remaining two were the comparison control group, the LPS group was dissolved in LPS in physiological saline and administered 1 μg (200 μl) intraperitoneally, and the comparative group was administered the same amount of physiological saline. . Changes in body temperature were photographed with a thermo camera every minute and stored on a laptop computer as a thermograph image. The maximum temperature of the back skin temperature was plotted over time from the thermograph image.
Experimental results :
As shown in the photograph in FIG. 5, the highest temperature was measured on the back skin in any mouse. In addition, as shown in the graph of FIG. 6, when the time-dependent change in temperature before LPS administration is plotted for each mouse, there is no large variation among individuals in any mouse, and the temperature tends to be low in the daytime and high in the nighttime. However, this measurement result is the result of measurement using a previously reported telemetry system (Reference 3: Kozak et al. Ann NY Acad Sci. 1998 Sep 29; 856: 33-47.) I found a very good match. From these facts, the body temperature of the mouse could be continuously measured with sufficient accuracy and reproducibility by this system.
Further, as shown in the graph of FIG. 7, in the LPS-administered mice, the body temperature of the LPS-administered mice is clearly increased under illumination, that is, in a simulated daytime environment, despite the low activity level. The body temperature change due to LPS administration could be measured with high accuracy. However, since the mice are nocturnal, there was no difference in body temperature between the control mice administered with physiological saline and the mice administered with LPS in an environment without illumination.

  According to the body temperature measurement system of the present invention, since a plurality of animals can be measured continuously and accurately while keeping them in the incubator in the same environment at the same time, the mouse whose body temperature is likely to fluctuate due to the influence of the environment Even small animals such as can stably measure changes in body temperature over time. As a result, it is possible to provide a novel means for accurately and simply examining body temperature, which is one of important physiological indicators in a wide range of technical fields such as medicine, pharmacy, and behavioral physiology.

1 Thermostatic chamber 2 Thermo camera A Small animal for experiment

Claims (11)

A thermostatic chamber capable of accommodating one or more experimental small animals;
A thermo camera that is an imaging device part of a thermography device capable of imaging the experimental small animal and displaying the temperature of the body surface as an image,
The thermostat has at least temperature and humidity control means capable of bringing the temperature and humidity suitable for the survival of small experimental animals in the tank, and ventilation means,
The thermo camera is arranged in the thermostat so that the small experimental animal can be imaged while being housed in the thermostat.
Body temperature measurement system for small laboratory animals.   The body temperature measuring system according to claim 1, wherein the thermostatic chamber further has an illuminating means that can be controlled so as to be able to irradiate light suitable for survival of a small experimental animal housed in the thermostatic chamber.   The body temperature according to claim 2, wherein the temperature, humidity, and illuminance in the bath can be controlled to the intended environment periodically or constantly by the temperature and humidity control means and the lighting means of the thermostatic bath. Measuring system.   The body temperature measuring system according to any one of claims 1 to 3, wherein the thermostatic bath further has a soundproof structure capable of suppressing the transmission of external sounds into the bath.   The body temperature measurement system according to any one of claims 1 to 4, further comprising a main body portion of a thermography device configured to analyze data of an image captured by the thermo camera and display the data as an image indicating a temperature distribution. .   Only one said thermo camera is arrange | positioned in the tank upper part of the said thermostat, It becomes the structure which images all the experimental small animals in a tank with this one thermo camera. The body temperature measurement system according to any one of the above.   A partition for partitioning the separate regions is provided at the bottom of the thermostat bath so that a plurality of small experimental animals can be accommodated in the thermostat bath separately in separate regions. Item 7. The body temperature measurement system according to any one of Items 1 to 6.   A storage container for storing the small experimental animal is provided at the bottom of the thermostatic chamber so as to be detachably fitted into the tank. The body temperature measurement system according to any one of claims 1 to 6, wherein the thermo camera can take an image of a small experimental animal housed in the body.   A partition for partitioning the separate regions is provided in the storage container so that a plurality of small laboratory animals can be stored separately in the storage container. 8. The body temperature measurement system according to 8. Using the body temperature measurement system according to any one of claims 1 to 9,
The temperature of the thermostat bath of the body temperature measurement system is set to a temperature and humidity suitable for the survival of the laboratory small animal, while the laboratory animal is kept in the bath, the laboratory animal is moved by the thermo camera of the body temperature measurement system. A method for measuring a body temperature for a small animal for experiment, which is characterized in that the temperature of the body surface of the small animal for experiment is obtained as an image based on the image data. The body temperature measurement system is the body temperature measurement system according to claim 3,
The body temperature measuring method according to claim 10, wherein the experimental small animal is imaged by the thermo camera while controlling the temperature, humidity, and illuminance in the tank periodically or constantly to an intended environment.