Surgical instrument and triggering method for aortic valve stenosis caused by guide wire injury

Abstract

The invention relates to a surgical instrument for aortic valve stenosis caused by guide wire injury and an initiation method, and belongs to the field of construction of animal models of diseases, and the surgical instrument comprises a bottom plate (1) used for placing a mouse; the mouse fixing assembly is arranged on the upper end face of the bottom plate (1) and used for fixing a mouse; the aortic valve injury assembly is arranged on the upper end face of the bottom plate (1) and used for injuring the aortic valve of the mouse. Compared with the prior art, the surgical instrument for treating aortic valve stenosis caused by guide wire injury is provided, and the modeling process of an aortic valve guide wire injury model is scientifically standardized through the surgical instrument.

Description

Technical Field

[0001] The present invention relates to the field of animal model construction for diseases, and in particular to a surgical instrument and a triggering method for aortic valve stenosis caused by guidewire damage. Background Art

[0002] Aortic stenosis is a progressive valvular heart disease characterized by structural alterations in the aortic valve due to congenital malformations, degeneration, or inflammation, resulting in restricted valvular opening and impaired left ventricular systolic hemodynamics. The core mechanism of aortic stenosis's pathological evolution is currently believed to be pathological remodeling triggered by left ventricular pressure overload. Its development involves two key components: first, persistent pressure overload caused by valvular calcification and stenosis, which promotes compensatory cardiomyocyte hypertrophy; and second, interstitial fibrosis and microcirculatory impairment caused by an imbalance in myocardial oxygen supply and demand under long-term mechanical stress, accompanied by abnormal activation of the renin-angiotensin-aldosterone system and the sympathetic nervous system. Dual intervention targeting both valvular structural abnormalities and ventricular remodeling has become an important therapeutic strategy in modern medicine, including valve replacement to relieve obstruction and anti-remodeling drug therapy. However, due to the limitations of human studies, the mechanisms of valvular calcification and the development of novel interventional devices still require systematic validation in mice.

[0003] Mice that can be widely used in the study of the disease mechanism and treatment of aortic stenosis should meet the following conditions: (1) reflect the main pathological mechanisms, symptoms, and signs of aortic stenosis; (2) the degree of simulation of aortic stenosis is controllable and has good reproducibility; (3) the genetic background information of the mice is complete; (4) the method of preparing the model is advanced and easy to carry out; (5) the experimental mice are economical and easy to raise. In actual research, there are two types of aortic stenosis mouse models: 1) using ApoE- / - mice and feeding them with a high-fat diet, and 2) injecting PCSK9 lentivirus into C57 mice and feeding them with a high-fat diet. The above two methods face the same problem: the modeling cycle is too long, with an average modeling time of 6 months, which greatly increases time and management costs. In addition, the above methods cannot well simulate the damage and treatment mechanism caused by the abnormal hemodynamics of the valve in the early stage and during the progression of the disease.

[0004] As described in patent CN117084820A, the aortic valve wire injury model (AVWI) delivers a guidewire to the aortic valve of mice through the carotid artery approach, and causes damage to the mouse aortic valve by rotating and pulling the guidewire, thereby inducing aortic valve stenosis in mice. This model simulates the underlying disease of aortic valve stenosis, abnormal anatomical features, and valve calcification, stenosis, myocardial remodeling, and heart failure caused by genetic defects, thereby studying the pathogenesis and treatment of these diseases. AVWI is an ideal model for restoring the pathophysiological development process of valve calcification and stenosis caused by valve damage, cardiac decompensation to heart failure, and the modeling cycle of this model is only about 3 months, which greatly shortens the modeling time. However, the AVWI modeling process is complicated, the degree of lesions is less controllable, and the model stability and repeatability need to be improved. At present, there is a lack of scientific and standardized AVWI modeling procedures and modeling auxiliary tools. Summary of the Invention

[0005] The purpose of the present invention is to provide a surgical instrument and a method for causing aortic valve stenosis caused by guidewire damage in order to overcome at least one of the above-mentioned defects of the prior art.

[0006] The purpose of the present invention can be achieved by the following technical solutions:

[0007] One of the purposes of the present invention is to provide a surgical instrument for treating aortic valve stenosis caused by guidewire damage, comprising:

[0008] Base plate for placing mice;

[0009] A mouse fixing assembly, which is provided on the upper surface of the bottom plate and is used to fix the mouse;

[0010] The aortic valve injury component is arranged on the upper end surface of the base plate and is used for injuring the aortic valve of mice.

[0011] Furthermore, the mouse fixing component includes a mouse fixing column, a groove is provided on the side of the mouse fixing column away from the mouse, and an elastic ring is provided on the mouse fixing column, one end of the elastic ring is in the groove, and the other end is connected to the upper incisor of the mouse.

[0012] Furthermore, the aortic valve injury component includes:

[0013] Guidewire fixed column;

[0014] A guide wire placement support, which is located on the upper end surface of the guide wire fixing column;

[0015] The guide wire is provided with a pair of limiting rings at intervals, and the wire body between the pair of limiting rings is placed on the guide wire placement support.

[0016] Furthermore, the guidewire fixing column includes:

[0017] A first column, which is arranged on the upper surface of the bottom plate and has a pair of mounting plates on its outer wall;

[0018] A second column is provided with a plurality of through holes spaced apart along its axial direction, and the guide wire placement support is located at an end of the second column away from the first column;

[0019] A locking structure includes a locking plate arranged between the pair of mounting plates and rotatably connected to the mounting plates, a second spring is provided between the locking plate and the outer wall of the first column, a locking column is provided at one end of the locking plate away from the mounting plate, and the locking column extends into the through hole to control the height of the second column extending out of the first column.

[0020] Furthermore, a first spring is provided in the first column, and one end of the second column located in the first column abuts against the first spring.

[0021] Furthermore, a scale is provided on the guide wire at one end close to the mouse.

[0022] Furthermore, the end of the guide wire near one end of the mouse is bent so as to damage the valve during rotation.

[0023] Furthermore, the bending amplitude of the end of the guide wire near the mouse is recorded as α, and α is in the range of 5°-30°.

[0024] Furthermore, a silicone ring is provided on the inner wall of the limiting ring, and the guide wire is sleeved on the silicone ring.

[0025] A second object of the present invention is to provide a method for inducing aortic valve stenosis, which is based on the surgical instrument described above and comprises the following steps:

[0026] S1. Place an anesthetized mouse in a supine position on a baseboard with its head near a mouse-fixing column. The mouse's limbs are fixed to the baseboard, and one end of the mouse's upper incisor is hooked to an elastic ring on the mouse-fixing column.

[0027] S2. Use ophthalmic scissors to make a 0.5-1 cm longitudinal incision in the midline of the mouse's neck and chest. Use ophthalmic forceps to gently separate the connective tissue and tissue on both sides of the tracheal midline. Use microtweezers to dissect the carotid artery and ligature the carotid artery. Cut the carotid artery, insert a guidewire, and untie the ligature.

[0028] S3. Insert the guidewire deep into the carotid artery until the end with the scale reaches the valve, record the depth of the guidewire insertion, continue to insert the guidewire until the guidewire reaches the apex of the heart, record the depth of the guidewire insertion again, determine the activity range based on the two guidewire immersion depths, determine the activity range and insert a pair of limit rings to limit the activity space, adjust the height of the guidewire fixing column, place the scale guidewire into the guidewire placement holder, rotate, and move the guidewire to damage the valve; withdraw the guidewire, ligate the carotid artery, and simply suture the muscle and skin intermittently. After disinfecting the wound with iodine, place it on a warming table to recover, and put it back into the cage after waking up to obtain an aortic valve guidewire injury model.

[0029] Compared with the prior art, the present invention has the following advantages:

[0030] (1) The present invention provides a surgical instrument for treating aortic valve stenosis caused by guidewire damage, and a scientific and standardized AVWI modeling process using the surgical instrument.

[0031] (2) The present invention provides a surgical instrument for aortic valve stenosis caused by guidewire damage. The mouse fixing assembly can firmly fix the mouse in a supine position through the cooperation of the mouse fixing column, groove and elastic ring, so that the mouse remains stable during the operation and the surgical error caused by the movement of the mouse is reduced; at the same time, the connection method between the elastic ring and the upper incisor of the mouse is simple and easy to operate, thereby improving the efficiency of surgical preparation.

[0032] (3) The present invention provides a surgical instrument for aortic valve stenosis caused by guidewire damage. The limiting rings arranged at intervals on the guidewire can effectively limit the active range of the guidewire, prevent the guidewire from being inserted too deeply or deviated, and improve the safety and accuracy of the surgical operation; the guidewire body near the mouse end is provided with a scale, which is convenient for the operator to accurately grasp the depth of guidewire insertion and ensure that the guidewire reaches the valve; the bending design and specific bending amplitude of the guidewire end enable it to more effectively damage the valve when rotated, thereby improving the success rate of modeling; the silicone ring on the inner wall of the limiting ring increases the friction between the guidewire and the guidewire, making the limiting ring less likely to slide, further ensuring the stability of the surgical operation.

[0033] (4) The present invention provides a method for inducing aortic valve stenosis. The inducing method based on the surgical instrument has clear, scientific and reasonable steps. From anesthesia and fixation of mice, to skin incision, tissue separation, guide wire insertion, valve damage, and postoperative treatment, each link has clear operating specifications and requirements, which can ensure the repeatability of the experiment and the success rate of modeling, thereby obtaining a stable and reliable aortic valve stenosis mouse model, providing an effective experimental animal model for the study of related diseases. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] Figure 1 A schematic diagram of a surgical instrument for aortic valve stenosis caused by guidewire damage in the present invention;

[0035] Figure 2 This is one of the partial enlarged views of the surgical instrument for aortic valve stenosis caused by guidewire damage in the present invention;

[0036] Figure 3 This is the second partial enlarged view of the surgical instrument for aortic valve stenosis caused by guidewire damage in the present invention;

[0037] Figure 4 This is one of the application scenarios of the surgical instrument for aortic valve stenosis caused by guidewire damage in the present invention;

[0038] Figure 5 This is the second application scenario diagram of the surgical instrument for aortic valve stenosis caused by guidewire damage in the present invention;

[0039] Figure 6 Aortic valve peak flow velocity (A) and valve tissue sections (B) of mice in the untreated control group (control group) and mice that underwent guidewire injury modeling surgery using the present invention (intervention group);

[0040] Figure 7 Comparison of aortic valve peak flow velocity (C), aortic valve area (D), valve calcification area (E), operation time (F), and survival rate (G) between mice in the conventional instrument group and mice that underwent guidewire injury modeling surgery using the present invention (improved instrument group);

[0041] The numbers in the figure are as follows: 1-base plate; 2-mouse fixing column; 3-groove; 4-guide wire fixing column; 401-first column; 402-second column; 403-through hole; 404-locking plate; 405-mounting plate; 406-first spring; 407-second spring; 5-guide wire placement support; 6-guide wire; 7-limiting ring; 8-elastic ring; 9-mouse. DETAILED DESCRIPTION

[0042] The present invention is described in detail below with reference to the accompanying drawings and specific embodiments. This embodiment is implemented based on the technical solution of the present invention, and provides a detailed implementation method and specific operation process, but the protection scope of the present invention is not limited to the following embodiments.

[0043] Example 1

[0044] This embodiment provides a surgical instrument for aortic valve stenosis caused by guidewire damage. The specific structure is shown in Figure 1-3 , including a base plate 1, a mouse fixation component, and an aortic valve injury component;

[0045] The base plate 1 is used to place mice; the mouse fixing component is arranged on the upper end surface of the base plate 1 and is used to fix mice; the aortic valve damage component is arranged on the upper end surface of the base plate 1 and is used to damage the aortic valve of mice.

[0046] Please see again Figure 1 In this embodiment, the mouse fixing assembly includes a mouse fixing column 2, the mouse fixing column 2 is provided with a groove 3 on the side away from the mouse, the mouse fixing column 2 is provided with an elastic ring 8, one end of the elastic ring 8 is in the groove 3, and the other end is connected to the upper incisor of the mouse. Figure 4 By cooperating with the mouse fixing column 2, the groove 3 and the elastic ring 8, the mouse can be firmly fixed in a supine position, so that the mouse remains stable during the operation and the surgical error caused by the movement of the mouse is reduced; at the same time, the connection method between the elastic ring and the upper incisor of the mouse is simple and easy to operate, which improves the efficiency of surgical preparation.

[0047] Please see again Figure 1 In this embodiment, the aortic valve injury assembly includes a guidewire fixing post 4, a guidewire placement holder 5, and a guidewire 6. The guidewire placement holder 5 is located on the upper end surface of the guidewire fixing post 4. A pair of limiting rings 7 are provided on the guidewire 6 at intervals, and the guidewire 6 is placed between the limiting rings 7 on the guidewire placement holder 5. The limiting rings 7 provided at intervals on the guidewire 6 effectively limit the range of movement of the guidewire 6, preventing the guidewire 6 from being inserted too deeply or deviating, thereby improving the safety and accuracy of the surgical procedure.

[0048] Please see again Figure 2-3 In this embodiment, the guidewire fixing column 4 includes a first column 401, a second column 402 and a locking structure;

[0049] The first column 401 is provided on the upper end surface of the base plate 1 and has a pair of mounting plates 405 on the outer wall; the second column 402 has a plurality of through holes 403 spaced apart along its axial direction, and the guide wire placement holder 5 is located at the end of the second column 402 away from the first column 401;

[0050] The locking structure includes a locking plate 404 arranged between the pair of mounting plates 405 and rotatably connected to the mounting plates 405, a second spring 407 is provided between the locking plate 404 and the outer wall of the first column 401, and a locking column is provided at one end of the locking plate 404 facing away from the mounting plate 405, and the locking column extends into the through hole 403 to control the height of the second column 402 extending out of the first column 401.

[0051] Please see again Figure 2-3In this embodiment, a first spring 406 is provided in the first column 401 , and one end of the second column 402 located in the first column 401 abuts against the first spring 406 .

[0052] Please see again Figure 1 In this embodiment, the guidewire 6 is provided with a scale on the end closest to the mouse. This scale facilitates the operator to accurately determine the depth of guidewire 6 insertion, ensuring that the guidewire reaches the valve. The guidewire scale corresponding to the valve opening to the apex is also measured. Subsequently, by adjusting the spaced limit rings 7, the guidewire can be prevented from being inserted too deeply or too shallowly, which could lead to model establishment failure.

[0053] Please see again Figure 1 In this embodiment, the end of the guide wire 6 near the end of the mouse is bent so as to damage the valve when rotating. The bending design and specific bending amplitude of the end of the guide wire 6 enable it to more effectively damage the valve when rotating, thereby improving the success rate of modeling.

[0054] In this embodiment, the bending amplitude of the end of the guide wire 6 near the end of the mouse is recorded as α, and α is in the range of 5°-30°.

[0055] In this embodiment, the upper end surface of the guide wire placement support is U-shaped.

[0056] In this embodiment, a silicone ring is provided on the inner wall of the limiting ring 7, which is sleeved on the guide wire 6. The silicone ring on the inner wall of the limiting ring increases the friction between the limiting ring and the guide wire, making the limiting ring less likely to slide, further ensuring the stability of the surgical operation.

[0057] Example 2

[0058] This embodiment provides a method for inducing aortic valve stenosis, which is based on the surgical instrument described in Example 1. For specific scenarios, see Figure 4-5 , the initiation method comprises the following steps:

[0059] S1. Anesthetize a mouse by intraperitoneal injection of 0.15 ml of 1% sodium pentobarbital. Place the anesthetized mouse 9 in a supine position on a base plate 1, with its head near the mouse-fixing column 2. Secure the mouse's limbs to the base plate 1 with medical tape, with one end of the mouse's upper incisor connected to an elastic ring 8 mounted on the mouse-fixing column 2.

[0060] S2. Use ophthalmic scissors to make a 0.5-1 cm longitudinal incision in the midline of the mouse's neck and chest. Use ophthalmic forceps to gently separate the connective tissue and tissue on both sides of the tracheal midline. Use microtweezers to dissect the carotid artery and ligature the carotid artery. Cut the carotid artery, insert a guidewire, and untie the ligature.

[0061] S3, guidewire 6 penetrates into the carotid artery, so that the end of guidewire 6 with the scale reaches the valve, record the depth of guidewire 6 immersion, continue to penetrate the guidewire 6, so that guidewire 6 reaches the apex of the heart, record the depth of guidewire 6 immersion again, determine the activity range according to the two guidewire immersion depths and insert a pair of limit rings 7 to limit the activity space, adjust the height of the guidewire fixing column 4, place the guidewire 6 into the guidewire placement holder 5, rotate, and move the guidewire 6 to damage the valve; withdraw the guidewire 6, ligate the carotid artery, suture the muscle and skin, disinfect the wound with iodine tincture, and place it on a warming table to recover. After mouse 9 wakes up, put it back into the cage to obtain an aortic valve guidewire injury model.

[0062] Figure 6 Aortic valve peak flow velocity (A) and valve tissue sections (B) of mice in the untreated control group (control group) and mice that underwent guidewire injury model surgery according to this example (intervention group); Figure 7 The aortic valve peak flow velocity (C), aortic valve area (D), valve calcification area (E), operation time (F), and survival rate (G) of mice in the conventional instrument group and mice that underwent guidewire injury modeling surgery using this example (improved instrument group) are compared.

[0063] Figure 6 The aortic valve peak flow velocity of mice in the model group was higher, the valve was thickened, and calcification was obvious. Figure 7 When the model was established using this embodiment, the aortic valve peak flow velocity of mice was higher, the aortic valve orifice area was smaller, the valve calcification area was larger, the surgical operation time was shorter, and the survival rate was higher.

[0064] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any other manner. Any person skilled in the art may utilize the above-disclosed technical content to modify or modify the present invention into equivalent embodiments. However, any simple modifications, equivalent variations, and modifications to the above embodiments that do not depart from the technical content of the present invention and are based on the technical essence of the present invention remain within the scope of protection of the present invention.

Claims

1. A surgical instrument for treating aortic valve stenosis caused by guidewire damage, characterized in that: include: a bottom plate (1) for placing mice; A mouse fixing assembly, which is arranged on the upper end surface of the bottom plate (1) and is used to fix the mouse; The aortic valve injury component is arranged on the upper end surface of the base plate (1) and is used for injuring the aortic valve of mice.

2. A surgical instrument for treating aortic valve stenosis caused by guidewire damage according to claim 1, characterized in that: The mouse fixing component comprises a mouse fixing column (2), wherein a groove (3) is provided on the side of the mouse fixing column (2) facing away from the mouse, and an elastic ring (8) is sleeved on the mouse fixing column (2), wherein one end of the elastic ring (8) is located in the groove (3) and the other end is connected to the upper incisor of the mouse.

3. A surgical instrument for treating aortic valve stenosis caused by guidewire damage according to claim 1, characterized in that: The aortic valve injury component comprises: Guide wire fixing column (4); A guide wire placement support (5) is located on the upper end surface of the guide wire fixing column (4); A guide wire (6) is provided with a pair of limiting rings (7) at intervals thereon, and the wire body between the pair of limiting rings (7) is placed on the guide wire placement support (5).

4. A surgical instrument for treating aortic valve stenosis caused by guidewire damage according to claim 3, characterized in that: The guide wire fixing column (4) comprises: A first column (401) is provided on the upper end surface of the base plate (1), and a pair of mounting plates (405) are provided on the outer wall of the first column; A second column (402) is provided with a plurality of through holes (403) spaced apart along its axial direction, and the guide wire placement support (5) is located at an end of the second column (402) away from the first column (401); A locking structure comprises a locking plate (404) arranged between the pair of mounting plates (405) and rotatably connected to the mounting plates (405), a second spring (407) being provided between the locking plate (404) and the outer wall of the first column (401), a locking column being provided at one end of the locking plate (404) facing away from the mounting plate (405), the locking column extending into the through hole (403) to control the height of the second column (402) extending out of the first column (401).

5. A surgical instrument for treating aortic valve stenosis caused by guidewire damage according to claim 4, characterized in that: A first spring (406) is provided in the first column (401), and one end of the second column (402) located in the first column (401) abuts against the first spring (406).

6. A surgical instrument for treating aortic valve stenosis caused by guidewire damage according to claim 4, characterized in that: The guide wire (6) is provided with a scale on one end thereof near the mouse.

7. A surgical instrument for treating aortic valve stenosis caused by guidewire damage according to claim 4, characterized in that: The end of the guide wire (6) near one end of the mouse is bent so as to damage the valve when rotating.

8. A surgical instrument for treating aortic valve stenosis caused by guidewire damage according to claim 7, characterized in that: The bending amplitude of the end of the guide wire (6) near the end of the mouse is recorded as α, and α is in the range of 5°-30°.

9. A surgical instrument for treating aortic valve stenosis caused by guidewire damage according to claim 2, characterized in that: The inner wall of the limiting ring (7) is provided with a silicone ring, which is sleeved onto the guide wire (6).

10. A method for inducing aortic valve stenosis, characterized in that: Based on the surgical instrument according to any one of claims 1 to 9, the triggering method comprises the following steps: S1. Place the anesthetized mouse in a supine position on a base plate (1), with its head on the side close to the mouse fixing column (2), the mouse's limbs fixed to the base plate (1), and one end of the mouse's upper incisor hooked to an elastic ring on the mouse fixing column (2); S2. Use ophthalmic scissors to make a longitudinal incision of 0.5 to 1 cm in the midline of the mouse's neck and chest. Use ophthalmic forceps to gently separate the connective tissue and tissues on both sides of the tracheal midline. Use microtweezers to dissect the carotid artery and ligature the carotid artery. Cut the carotid artery, insert a guide wire (6), and untie the ligature. S3, the guide wire (6) is inserted into the carotid artery, so that the end of the guide wire (6) with the scale reaches the valve, the depth of the guide wire (6) is recorded, the guide wire (6) is further inserted into the guide wire (6) so that the guide wire (6) reaches the apex of the heart, and the depth of the guide wire (6) is recorded again. The activity range is determined according to the two guide wire immersion depths and a pair of limiting rings (7) are inserted to limit the activity space, the height of the guide wire fixing column (4) is adjusted, the guide wire (6) is placed in the guide wire placement support (5), rotated, and the guide wire (6) is moved to damage the valve; the guide wire (6) is withdrawn, the carotid artery is ligated, the muscles and skin are sutured, the wound is disinfected with iodine tincture, and then placed on a warming table for recovery. After waking up, the cage is returned to obtain an aortic valve guide wire injury model.

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