JP5773486B2 - Laboratory animal muscle strength measurement device - Google Patents

Description

  The present invention relates to providing an apparatus for measuring muscle strength of a laboratory animal (eg, mouse, rat).

  When elucidating the pathological mechanism of diseases characterized by decreased muscular strength (for example, muscular dystrophy and polymyositis), or developing therapeutic methods and drugs for these diseases, disease model animals (for example, Research using disease model mice and the like has been conducted. Therefore, it is very important to objectively evaluate the pathological condition of these disease model animals when elucidating the pathological mechanism of these diseases or developing therapeutic methods and drugs for these diseases.

  Conventionally, anatomical and pathological techniques have been mainly employed as means for confirming pathological changes in elucidating pathological mechanisms or developing therapeutic methods and drugs for these diseases. When such a conventional method is adopted, in order to evaluate pathological changes, a large number of disease model animals are prepared, and anatomical and pathological tissue sections are prepared over time and evaluated. I went. However, even if it is established as a disease model animal, each individual has a different pathological condition, and it is very difficult to accurately examine the pathological change. In addition, it has been difficult to analyze pathological conditions accompanying changes over time such as gene therapy.

  On the other hand, devices for measuring the muscle strength of experimental animals have been developed so far. For example, the experimenter holds the body of the rat / mouse, and the forelimb or limb is held by the grid-like network structure of the device or the wire bar, and then the rat / mouse is pulled. There was a device that measured the maximum tension when the forelimbs or limbs separated from the reticulated structure and evaluated this as muscle strength (Grip Strength Meter (Columbus Instruments, http://www.colinst.com /brief.php?id=36), Grip Strength Meter for Mouse (Ugo Basile Srl, http://www.ugobasile.com/catalogue/product/47106_grip_strength_meter_for_mouse.html)). However, in these devices, it is necessary to hold the rat or mouse on the reticulated structure or the wire bar, and it is necessary to train the animal in order to hold it. In addition, there are drawbacks in that the objectivity of measurement is lacking, such as stress applied to the animal during measurement, or the force that is caught when the animal is excited. As a result, there are problems such as whether or not measurement is possible depending on the experience of the experimenter.

  However, until now, no method has been developed that can objectively measure muscle strength while reducing stress on animals.

  An object of the present invention is to develop a method for measuring muscle strength by using the instinct habit of experimental animals such as mice and rats so as not to give stress to the experimental animals during measurement.

  The inventor of the present invention has developed a method capable of measuring the muscle strength of the extremities while reducing the stress applied to the animal as the subject. Specifically, the step of engaging the subject and the muscle strength measuring member with the connecting member; the step of introducing the subject into the cylindrical member that accommodates the subject; the subject passing through the cylindrical member with the muscle strength measuring member Has developed a method for measuring the muscle strength of a subject, comprising the step of measuring the muscle strength of the subject by moving to the opposite side. The inventors of the present invention have also clarified that the above-described method can be realized by making a unique device. Specifically, the muscle strength of the subject including: a cylindrical member that accommodates the subject; a muscle strength measuring member that measures the muscle strength of the subject; and a connecting member that engages the subject and the muscle strength measuring member; A measuring device was developed.

  By using the apparatus of the present invention, accurate and continuous muscle strength measurement can be performed while applying as little stress as possible to experimental animals (for example, mice and rats). In addition, muscle strength measurement can be performed even in an animal having a disorder in the extremity of the limb or in which the disorder has developed.

FIG. 1 is a diagram showing an embodiment of a muscle strength measuring apparatus for experimental animals according to the present invention. FIG. 2 is a diagram showing another embodiment of the muscle strength measuring apparatus for experimental animals of the present invention. FIG. 3 is a diagram showing muscle strength (N) measured using the apparatus of the embodiment of FIG. FIG. 4 is a diagram showing an example of the study of the structure of the cylindrical member.

  In one aspect, the present invention provides a method capable of measuring limb muscle strength while reducing stress applied to an animal as a subject. Specifically, the present invention includes a step of engaging a subject and a muscle strength measuring member with a connecting member; a step of introducing the subject into a cylindrical member that accommodates the subject; A method for measuring the muscle strength of a subject is provided, including the step of measuring the muscle strength of the subject by moving to a side opposite to the muscle strength measuring member.

  The present invention provides a disease model animal (for example, a disease model mouse, etc.) that could not be obtained so far in various studies related to a disease (for example, muscular dystrophy, polymyositis, etc.) characterized by a decrease in muscle strength. The objective of the test is any disease model animal for a disease characterized by reduced muscle strength. Examples of animals that can be used as such disease model animals include animals such as mice, rats, guinea pigs, rabbits, gerbils, and musk rats. Of these, mice and rats, which are rich in types of disease model animals, are particularly preferred as test subjects.

  The method of the present invention is characterized in that the muscle strength is measured using the instinctive behavior of the experimental animal. As a result, the stress on the experimental animal during the measurement of the muscle strength can be greatly reduced, and the experimenter's Variations with experience values can be reduced, and the muscle strength of experimental animals can be measured more objectively.

  Many animals tend to prefer spaces where their bodies can fit as instinctual habits, and have the habit of calming down in such spaces. For example, mice, rats, and the like tend to prefer to spend time there by creating a nest-like space with wood chips near the wall of the nest box under the breeding conditions in the laboratory. The first feature of the present invention is to introduce the experimental animal into a cylindrical member adapted to the size of the experimental animal by utilizing such a property that favors a narrow space. Since an animal actively enters such a cylindrical member and moves toward the back of the cylindrical member, the force at the time of this entry is measured.

  In addition, many animals have a habit of preferring dark places, and based on such a habit, a cover is attached around the cylindrical member described above, or depending on the material of the cylindrical member, The surroundings may be invisible.

  In the present invention, the cylindrical member may be any material provided with durability suitable for animal breeding and easy cleaning, and is composed of a metal material or a plastic material. Is done. As the plastic material, polyethylene, polypropylene, polyvinyl chloride, polystyrene, polyvinyl acetate, polytetrafluoroethylene, acrylonitrile butadiene styrene resin, acrylonitrile-styrene resin, acrylic resin, and the like can be used.

  The inner surface of the cylindrical member needs to be provided with a structure that serves as a foothold when the experimental animal enters with its own intention. This is because if the surface is smooth, the animal slips when entering, and accurate muscle strength cannot be recorded. Therefore, the structure provided on the inner surface of the cylindrical member of the present invention can be selected from the group consisting of a network structure, an uneven structure, and a scale structure.

  In a disease characterized by a decrease in muscle strength, muscles at the tip of the limbs are damaged and muscle strength is reduced, but muscles near the trunk may not be damaged. In such a case, the structure of the inner surface of the tubular member is selected so that a portion closer to the trunk, such as a heel, is applied to the tubular member and the muscle strength of the portion closer to the trunk can be exerted. be able to. For example, when a mesh structure is used as the internal structure, the mesh size of the mesh structure can be changed as shown in FIG.

  The cylindrical member may have any cross-sectional shape as long as the subject animal can enter and can be formed from the viewpoint of the material of the cylindrical member and its surface structure. For example, the cross-sectional shape of the cylindrical member may be any structure such as a polygonal structure such as a triangle, a quadrangle, a pentagon, and a hexagon, a circle, or an ellipse.

  Next, the muscular strength measuring member is engaged with the animal that enters the inside of the cylindrical member via the connecting member. In the conventional method, since the experimenter directly held the animal, unnecessary stress was applied to the animal, and objective muscle strength measurement could not be performed. By engaging the animal with the muscle strength measuring member, the stress on the animal can be greatly reduced. Here, the connecting member that engages between the animal and the muscle strength measuring member transmits the muscle strength exerted by the animal (that is, the tension generated when entering the cylindrical member) to the muscle strength measuring member. Therefore, the connecting member may be a non-stretchable string-like structure or a string-like structure having a stretchability that can absorb an impact. Moreover, it is preferable to use a metal wire or chain as the connecting member in consideration of the habit of animals that bite or try to remove the one engaged with the body. For the purpose of further reducing the stress applied to the animal, the attachment portion of the connecting member to the subject may further include an engaging holder. Such a holder can be prepared using a silicon tube, a rubber tube or the like.

  The muscular strength measurement member may be any device that can measure the tension generated when the animal enters the cylindrical member. For example, the muscular strength measurement device, the kinetic energy measurement device, Etc. can be used. Devices that can be used as tension measuring devices include tension transducers that convert tension into electrical signals, devices that measure the distance traveled by animals under constant tension, and animals under constant tension. Examples thereof include an apparatus for measuring the kinetic energy of the apparatus, an apparatus for measuring a maximum tension and a change in tension over time, and the like.

  In another aspect, the present invention also provides an apparatus for implementing the above-described method for measuring the muscle strength of a subject. Specifically, the present invention includes a cylindrical member that accommodates the subject; a muscle strength measuring member that measures the muscle strength of the subject; and a connecting member that engages the subject and the muscle strength measuring member; An apparatus for measuring muscle strength of a subject is provided.

  FIG. 1 is a diagram showing an embodiment of the muscle strength measuring apparatus according to the present invention. In FIG. 1, a muscle strength measuring device having a cylindrical member 1, a muscle strength measuring member 2, and a connecting member 3 for engaging the subject and the muscle strength measuring member 2 is shown. In the embodiment shown in this figure, the muscle strength measuring member 2 is a tension transducer.

  FIG. 2 is a diagram showing an embodiment of the muscle strength measuring device according to the present invention. FIG. 2 shows a muscle strength measuring device having a cylindrical member 1, a muscle strength measuring member 4, and a connecting member 3 for engaging the subject with the muscle strength measuring member 4. In the embodiment shown in this figure, the muscle strength measuring member 4 is a device that measures the moving distance of an animal with a constant tension applied.

  In both FIG. 1 and FIG. 2, the animal enters the cylindrical member 1 in the direction of the arrow, and tension is applied to the connecting member 3. And as a result, in FIG. 1, the tension is transmitted to the tension transducer 2 connected at the other end to the connecting member 3 attached to the experimental animal, and the tension transducer 2 converts the tension into an electrical signal. The tension can be quantified. On the other hand, in FIG. 2, the connecting member 3 attached to the experimental animal is connected to the weight 5 at the other end, and the distance that the weight 5 moves due to tension is measured by a device that measures the moving distance, such as a tachometer 4. Thus, the tension can be quantified.

Example 1 Muscle Strength Measuring Device Using Tension Transducer In this example, a muscle strength measuring device using a tension transducer was manufactured as a muscle strength measuring device, and the muscle strength of a mouse was measured.

  As the cylindrical member, a metal net having a fine mesh was formed into a cylindrical shape and used. As a connecting member that connects the mouse and the tension transducer, a metal wire was used, one end of which was connected to the mouse tail and the other end was connected to the tension transducer. When connecting a metal wire to the mouse's tail, a silicon tube was inserted into the tail and engaged with the metal wire between the tail and the silicon tube so as not to stress the mouse. (See Figure 1).

  The mouse entered the cylindrical member and proceeded with its interior facing away from the entrance. As a result, the connecting member became tensioned, and the tension was transmitted to the tension transducer. This tension transducer calculated the tension value as Newton (N) by converting the tension into a voltage and converting it.

  FIG. 3 shows the results of actually measuring muscle strength using five mice as subjects using this apparatus. In this figure, the results for each of the five mice are shown as No. 1 to No. 5, and the upper part of each figure shows the maximum tension and the lower part shows the acceleration, respectively. In all of these No. 1 to No. 5 mice, it was possible to measure the maximum tension of 2.38 N to 2.80 N, indicating that the maximum muscle strength can be measured almost stably.

Example 2: Muscle strength measuring device by measuring the moving distance of a weight In this example, a muscle strength measuring device using a device for measuring the moving distance of an animal in a state where a constant tension is applied is produced as a muscle strength measuring device. Then, the muscle strength of the mice was measured.

  As the cylindrical member, a metal net having a fine mesh was formed into a cylindrical shape and used. As a connecting member connecting the mouse and the tension measuring member, a metal wire was used, one end of which was connected to the mouse's tail and the other end was connected to the weight. When connecting a metal wire to the mouse's tail, a silicon tube was inserted into the tail and engaged with the metal wire between the tail and the silicon tube so as not to stress the mouse. (See Figure 2).

  The mouse entered the cylindrical member and proceeded with its interior facing away from the entrance. As a result, the metal wire connected to the weight became tensioned, and the weight further moved when the mouse further entered the cylindrical member. The amount of work of the mouse was calculated by measuring this moving distance.

Example 3: Examination of the structure of the cylindrical member In this example, it was examined whether the size of the mesh of the cylindrical member had an effect on exerting the muscle strength of the mouse.

  In this example, two types of nets, a metal net with a fine mesh and a metal net with a coarse mesh, were prepared, and a cylindrical member was molded using these. The fine mesh is the size of the mesh that catches the toes (nails) of the mouse limbs (Fig. 4 (a)), while the coarse mesh is the size of the mesh that catches the heel of the mouse (Fig. 4 (b)). . Using these nets, an apparatus similar to that in Example 1 was produced.

  As a result, no matter which mesh was used, the mesh was used to generate a thrust force on the side opposite to the entrance, and as a result, the same tension could be transmitted to the tension transducer.

  The apparatus of the present invention can perform accurate and continuous muscle strength measurement while reducing the stress applied to experimental animals (for example, mice and rats), and can also measure muscle strength even in animals that develop disorders at the extremities. To elucidate the pathological mechanism of diseases characterized by decreased muscle strength (for example, muscular dystrophy and polymyositis), or develop therapeutic methods and drugs for these diseases The practical muscle strength of a disease model animal (eg, a disease model mouse) can be measured.

Claims (14)

An apparatus for measuring muscle strength of a subject, including:
A cylindrical member containing the subject;
A muscle strength measuring member for measuring the muscle strength of the subject; and a coupling member for engaging the subject with the muscle strength measuring member;
Only including, where the subject is an animal selected from experimental animals and disease model animal, the muscular strength measuring device. Wherein the animal is a mouse or rat, the subject of the muscular strength measuring device of claim 1. 3. The apparatus for measuring muscle strength of a subject according to claim 1, wherein the inner surface of the cylindrical member is composed of a network structure, a concavo-convex structure, or a scale structure. Cross-sectional shape of the tubular member, a polygonal structure, circular or elliptical, constituted by the subject muscle strength measuring device according to any one of claims 1 to 3. The muscle strength measuring device for a subject according to any one of claims 1 to 4 , wherein the muscle strength measuring member is selected from a tension measuring device, a kinetic energy measuring device, and a device that measures a maximum tension and a change in tension over time. . Connecting member is a string-like structure of the non-stretchable, subject muscle strength measuring device according to any one of claims 1-5. 7. The apparatus for measuring muscle strength of a subject according to any one of claims 1 to 6 , further comprising an engaging holder in an attachment portion of the connecting member to the subject. A method for measuring muscle strength of a subject, comprising:
Engaging the subject and the muscle strength measuring member with a connecting member;
Introducing the subject into a cylindrical member containing the subject;
Measuring the muscle strength of the subject by moving the subject through the cylindrical member to the opposite side of the muscle strength measuring member;
Unrealized, the subject is an animal selected from experimental animals and disease model animal, a method for measuring the strength of the. 9. The method for measuring muscle strength of a subject according to claim 8 , wherein the animal is a mouse or a rat. 10. The method for measuring muscle strength of a subject according to claim 8 or 9 , wherein the inner surface of the cylindrical member is composed of a network structure, an uneven structure, and a scale structure. 11. The method for measuring muscle strength of a subject according to any one of claims 8 to 10 , wherein a cross-sectional shape of the cylindrical member is constituted by a polygonal structure, a circle, or an ellipse. 12. The muscular strength measurement member is selected from a tension measurement device, a kinetic energy measurement device, and a device that measures changes in maximum tension and tension over time, and measures muscle strength of a subject according to any one of claims 8 to 11. How to do. The method for measuring muscle strength of a subject according to any one of claims 8 to 12 , wherein the connecting member is a non-stretchable string-like structure. 14. The method for measuring muscle strength of a subject according to any one of claims 8 to 13 , further comprising an engaging holder in an attachment portion of the connecting member to the subject.