System for constructing tricuspid regurgitation model of transjugular vein rat and application of system

Abstract

The invention provides a system for constructing a tranjugular vein rat tricuspid regurgitation model and application thereof, and belongs to the technical field of tricuspid regurgitation diseases. The system for constructing the tricuspid regurgitation model of the transjugular vein rat comprises an anesthesia article, an incision forming article, a stent conveying system, a coronary artery stent system, a balloon dilatation system, echocardiography examination equipment, an incision suturing article and a postoperative care article, wherein the incision forming article is used for making an incision of 1-2 cm in the rat. Through the system, a tricuspid regurgitation model can be constructed for a rat, and an incision of 1-2cm can be formed for the rat by using the incision forming article, so that the trauma is small, the operation can be performed under common laboratory conditions, and the whole system is relatively low in manufacturing cost and easy to popularize. Compared with existing thoracotomy modeling, the rat tricuspid valve regurgitation model construction through the system is easy to operate, low in cost and easy to popularize in a large area in laboratories with general conditions.

Description

Technical Field

[0001] The present invention relates to the technical field of tricuspid valve regurgitation disease, and in particular to a system for constructing a transjugular rat tricuspid valve regurgitation model and an application thereof. Background Art

[0002] At present, there are few basic studies on tricuspid regurgitation disease. One of the important reasons is the lack of feasible, stable and economical tricuspid regurgitation models. The existing tricuspid regurgitation models include regurgitation models of large animals such as goats, dogs and pigs. These technologies create tricuspid regurgitation by removing the tricuspid valve leaflets and destroying the tricuspid valve key (references: PMID: 26558988; PMID: 37615887; establishing a tricuspid regurgitation model through a small right atrium incision). These models require open-chest surgery, which is more traumatic, more expensive, and more complicated to operate. They require more human and material support, and cannot be widely promoted in laboratories under general conditions. They can only be operated in professional animal experimental centers. Summary of the invention

[0003] The present invention is made to solve the above-mentioned problem, and aims to provide a system for constructing a transjugular rat tricuspid regurgitation model and its application.

[0004] The present invention provides a system for constructing a transjugular rat tricuspid regurgitation model, which has the following characteristics: anesthesia supplies, incision forming supplies, a stent delivery system, a coronary stent system, a balloon dilatation system, an echocardiography device, incision suturing supplies, and postoperative care supplies. The incision forming supplies are used to make an incision of 1-2 cm in size on rats.

[0005] The system for constructing a transjugular rat tricuspid regurgitation model provided by the present invention may also have the following features: wherein, anesthetic supplies include anesthetics and anesthetic needles, the anesthetic is 1% sodium pentobarbital, incision forming supplies include surgical scissors, tweezers, disinfectant and sterile drapes, incision suturing supplies include suture needles and sutures, and postoperative care supplies include glucose sodium chloride injection and a rewarming blanket.

[0006] The system for constructing a transjugular rat tricuspid regurgitation model provided by the present invention may also have the following characteristics: wherein the rats are adult rats, and the adult rats are 70-day-old rats.

[0007] The system for constructing a transjugular rat tricuspid regurgitation model provided by the present invention may also have the following features: wherein, the stent delivery system includes a guide sheath assembly and a guide wire, the guide sheath assembly includes a guide sheath and an injection needle, the injection needle is removably arranged on the guide sheath, and the guide wire is adapted to the guide sheath and is used to be guided into the rat heart through the guide sheath.

[0008] The system for constructing a transjugular rat tricuspid regurgitation model provided by the present invention may also have the following features: wherein the coronary stent system is a platinum-chromium alloy coronary stent system, and the balloon dilatation system includes a balloon and a balloon dilatation pressure pump.

[0009] The system for constructing a transjugular rat tricuspid regurgitation model provided by the present invention may also have the following features: wherein the diameter of the guide sheath is 0.075 mm, the diameter of the guide wire is 0.007 mm, and the outer diameter of the stent after the coronary stent system is released is 3.33 mm.

[0010] The system for constructing a transjugular rat tricuspid regurgitation model provided by the present invention may also have the following features, further comprising: wherein the shaving supplies include a razor.

[0011] The present invention also provides application of the system for constructing a transjugular rat tricuspid valve regurgitation model in constructing a transjugular rat tricuspid valve regurgitation model.

[0012] The application provided by the present invention may also have such a feature, comprising the following steps:

[0013] Step 1, use anesthetics to perform general anesthesia on the rats through intraperitoneal injection, then remove the hair on the neck and chest of the rats, treat them with iodine disinfectant, and then cover the neck and chest areas with sterile drapes to establish a sterile area for surgery;

[0014] Step 2, using surgical scissors to make an incision on the right neck of the rat to expose the right jugular vein, then inserting the guide sheath assembly of the stent delivery system into the right jugular vein, pulling out the needle of the guide sheath assembly, leaving the guide sheath of the guide sheath assembly in the right jugular vein, then inserting the guide wire of the stent delivery system through the guide sheath into the right heart, and pulling out the guide sheath;

[0015] Step 3, using an echocardiography device to take a thoracic echocardiogram of the rat, under the guidance of the transthoracic echocardiogram, the coronary stent system is delivered to the tricuspid valve ring along the guide wire, after confirming that the stent is located at the tricuspid valve, the balloon expansion pressure pump of the balloon expansion system is used to release the stent, the pressure is 15 kPa, and then the liquid in the balloon is released, the guide wire is completely withdrawn, and finally the puncture site is pressed for 3-5 minutes to stop bleeding and the incision is sutured with an incision suture product;

[0016] Step 4, after the operation, postoperative care products were used for fluid replacement and rewarming. At 4 and 8 weeks after the operation, cardiac ultrasound examination revealed tricuspid valve regurgitation, thereby obtaining a transjugular rat tricuspid valve regurgitation model.

[0017] The application provided by the present invention may also have the following feature: wherein the tip of the guide wire is molded into a curled shape before introduction, thereby preventing the guide wire from entering the inferior vena cava.

[0018] Functions and Effects of the Invention

[0019] According to the system for constructing a transjugular rat tricuspid regurgitation model and its application involved in the present invention, because the system includes anesthesia supplies, incision forming supplies, a stent delivery system, a coronary stent system, a balloon dilatation system, echocardiography equipment, incision suturing supplies, and postoperative care supplies, a tricuspid regurgitation model can be constructed for rats through the system, and because a 1-2 cm incision can be made on the rat using the incision forming supplies, the trauma is small and the operation can be performed under ordinary laboratory conditions. The cost of the entire system is low. Compared with the existing open-chest modeling, the construction of a rat tricuspid regurgitation model using the system is simple to operate and low in cost, and is easy to promote on a large scale in laboratories under general conditions. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 These are photos of the process of constructing a transjugular rat tricuspid regurgitation model using the system for constructing a transjugular rat tricuspid regurgitation model in an embodiment of the present invention, wherein Figure A shows the exposure of the jugular vein, Figure B shows the puncture and insertion of the sheath, Figure C shows the insertion of the guide wire, Figure D shows the insertion of the balloon stent, Figure E shows ultrasound guidance, and Figure F shows the release of the stent.

[0021] Figure 2 These are cardiac ultrasound photographs after surgery of a transjugular rat tricuspid regurgitation model (TR model) constructed using a system for constructing a transjugular rat tricuspid regurgitation model in an embodiment of the present invention, wherein Figure A, Figure B, and Figure C are taken before surgery and 4 weeks and 8 weeks after surgery, respectively. Figure 3 These are the heart photos, HE staining pictures of heart paraffin sections and WGA staining pictures 8 weeks after the TR model was constructed in the embodiment of the present invention, wherein sham is the sham operation group and TR is the experimental group.

[0022] Figure 4 The figures are Sirius Red staining and Masson staining of cardiac paraffin sections 8 weeks after the TR model was constructed in the embodiment of the present invention, wherein sham is a sham operation group and TR is an experimental group. Figure 5 The figures are the appearance and ultrasound images of rats 8 weeks after the TR model was constructed in the embodiment of the present invention, wherein sham is the sham operation group and TR is the experimental group.

[0023] Figure 6 This is a statistical table of body weight and organ weights of rats 8 weeks after the TR model was constructed in the embodiments of the present invention.

[0024] Figure 7Table 1 is the statistical results of cardiac ultrasound before and 4 and 8 weeks after the TR model was constructed in the embodiment of the present invention, *P<0.05; **P<0.01; ***P<0.001; ****p<0.0001; RVEDV: right ventricular end-diastolic volume; RVESV: right ventricular end-systolic volume; RA: right atrium.

[0025] Figure 8 Table 2 is the statistical results of cardiac ultrasound before and 4 and 8 weeks after the TR model was constructed in the embodiment of the present invention, *P<0.05; **P<0.01; ***P<0.001; ****p<0.0001; LVEF: left ventricular ejection fraction; FAC: right ventricular area change fraction; TAPSE: tricuspid annular systolic motion amplitude. DETAILED DESCRIPTION

[0026] In order to make the technical means, creative features, objectives and effects achieved by the present invention easy to understand, the following embodiments and the accompanying drawings specifically illustrate the system for constructing a transjugular rat tricuspid regurgitation model and its application.

[0027] Example

[0028] This embodiment provides a system for constructing a transjugular rat tricuspid regurgitation model, including: anesthesia supplies, shaving supplies, incision formation supplies, stent delivery system, coronary stent system, balloon dilatation system, echocardiography equipment, incision suturing supplies, and postoperative care supplies.

[0029] Among them, the anesthetic supplies include anesthetics and anesthetic needles. The anesthetic is 1% sodium pentobarbital and the anesthetic needle is a general anesthetic needle for rats. The incision forming supplies include surgical scissors, tweezers, iodine disinfectant and sterile drapes. The surgical scissors are used to make 1-2 cm incisions on rats. Shaving supplies include razors.

[0030] The stent delivery system includes a guide sheath assembly and a guide wire. The guide sheath assembly includes a guide sheath and an injection needle, the injection needle (24G) is removably arranged on the guide sheath, and the guide wire is adapted to the guide sheath and is used to guide into the rat heart through the guide sheath. The diameter of the guide sheath is 0.075 mm, and the diameter of the guide wire is 0.007 mm. The stent delivery system is a commercially available product.

[0031] The coronary stent system is a platinum-chromium alloy coronary stent system, and the balloon dilatation system includes a balloon and a balloon dilatation pressure pump. The outer diameter of the stent after the coronary stent system is released is 3.33 mm. These are commercially available products.

[0032] The echocardiography equipment was used to perform echocardiography on rats.

[0033] Supplies for incision closure include needles and sutures. Postoperative care supplies include glucose and sodium chloride injection and rewarming blankets.

[0034] The present invention also provides a method for constructing a transjugular rat tricuspid regurgitation model using the system for constructing a transjugular rat tricuspid regurgitation model. The rats used in the method are 70-day-old rats provided by Sibeifu (Suzhou) Biotechnology Co., Ltd.

[0035] Figure 1 These are photos of the process of constructing a transjugular rat tricuspid regurgitation model using the system for constructing a transjugular rat tricuspid regurgitation model in an embodiment of the present invention, wherein Figure A shows the exposure of the jugular vein, Figure B shows the puncture and insertion of the sheath, Figure C shows the insertion of the guide wire, Figure D shows the insertion of the balloon stent, Figure E shows ultrasound guidance, and Figure F shows the release of the stent.

[0036] like Figure 1 As shown, the method for constructing a transjugular rat tricuspid regurgitation model using the above system comprises the following steps:

[0037] Step 1, rats were anesthetized by intraperitoneal injection of 1% sodium pentobarbital (1g / 100ml), and the body temperature was maintained at 37°C. Under general anesthesia, the rats were placed supine on the operating table. The hair on the neck and chest of the rats was then removed and treated with iodine disinfectant, and then the neck and chest area was covered with a sterile drape to establish a sterile field for surgery.

[0038] Step 2: Use surgical scissors to make an incision on the right side of the rat's neck to expose the right jugular vein ( Figure 1 A) and then insert the introducer sheath assembly of the stent delivery system into the right jugular vein ( Figure 1 B), remove the needle of the guide sheath assembly, leaving the guide sheath in the right jugular vein, and then pass the guide wire of the stent delivery system through the guide sheath into the right heart. The tip of the guide wire is curled before introduction to prevent the guide wire from entering the inferior vena cava. Then, remove the guide sheath ( Figure 1 C).

[0039] Step 3, using an echocardiography device to take a thoracic echocardiogram (TEE) of the rat, under the guidance of transthoracic echocardiography ( Figure 1 E) The coronary stent system is inserted into the tricuspid valve ring along the guide wire ( Figure 1 D). The position of the coronary stent system can be adjusted before release. After confirming that the stent is located in the tricuspid valve, the balloon expansion pressure pump of the balloon expansion system is used to release the stent ( Figure 1 F), the pressure is 15kPa, and the outer diameter of the stent after release can reach 3.33mm. Then release the liquid in the balloon, withdraw the guide wire completely, and finally press the puncture site for 3-5 minutes to stop bleeding and suture the incision with a needle and suture.

[0040] Step 4: After surgery, the rats were rehydrated with glucose and sodium chloride injection, rewarmed with a rewarming blanket, and their physical signs were monitored. Eight weeks after surgery, tricuspid regurgitation was detected by cardiac ultrasound, thereby obtaining a transjugular rat tricuspid regurgitation model.

[0041] In addition, the rats were euthanized eight weeks after surgery, and tissues including the heart, kidney, liver, and spleen were obtained for pathological analysis.

[0042] Figure 2 These are cardiac ultrasound photographs after surgery of a transjugular rat tricuspid regurgitation model (TR model) constructed using a system for constructing a transjugular rat tricuspid regurgitation model in an embodiment of the present invention, wherein Figure A, Figure B, and Figure C are taken before surgery and 4 weeks and 8 weeks after surgery, respectively.

[0043] like Figure 2 As shown, tricuspid regurgitation has been successfully demonstrated in the TR model by cardiac ultrasound at 4 and 8 weeks after surgery.

[0044] Figure 3 These are the heart photos, HE staining pictures of heart paraffin sections and WGA staining pictures taken 8 weeks after the TR model was constructed in the embodiment of the present invention, wherein sham is the sham operation group and TR is the experimental group.

[0045] like Figure 3 As shown, 8 weeks after surgery, the hearts of rats in the TR model group were significantly larger than those in the control group.

[0046] Figure 4 The figures are Sirius Red staining and Masson staining of cardiac paraffin sections 8 weeks after the TR model was constructed in the embodiment of the present invention, wherein sham is a sham operation group and TR is an experimental group.

[0047] like Figure 4 As shown, 8 weeks after surgery, the heart of the TR model group had obvious fibrosis changes compared with the control group (sham) (A). In addition, the liver (B), spleen (C), and kidney (D) of the TR model group had more obvious fibrosis than the control group.

[0048] Figure 5 The figures are the appearance and ultrasound images of rats 8 weeks after the TR model was constructed in the embodiment of the present invention, wherein sham is the sham operation group and TR is the experimental group.

[0049] like Figure 5 As shown, 8 weeks after surgery, the rats in the TR model group showed skin color changes (right B), a large amount of ascites (D), and widened hepatic veins (F), indicating that the TR rat model was successfully established.

[0050] Figure 6This is a statistical table of organ weights of rats 8 weeks after the TR model was constructed in the embodiments of the present invention.

[0051] like Figure 6 As shown, the body weight and organ weights of 6 rats in the TR group and 6 rats in the control group were compared 8 weeks after surgery. It was found that the body weight, heart weight and liver weight of the rats in the TR model group were significantly increased.

[0052] Figure 7 Table 1 is the statistical results of cardiac ultrasound before and 4 and 8 weeks after the TR model was constructed in the embodiment of the present invention, *P<0.05; **P<0.01; ***P<0.001; ****p<0.0001; RVEDV: right ventricular end-diastolic volume; RVESV: right ventricular end-systolic volume; RA: right atrium.

[0053] like Figure 7 As shown, 6 rats in the TR group were implanted with coronary stents. Cardiac ultrasound was performed at 4 and 8 weeks of follow-up, showing that the hearts of the rats were significantly enlarged at 4 and 8 weeks compared with the baseline indicators.

[0054] Figure 8 Table 2 is the statistical results of cardiac ultrasound before and 4 and 8 weeks after the TR model was constructed in the embodiment of the present invention, *P<0.05; **P<0.01; ***P<0.001; ****p<0.0001; LVEF: left ventricular ejection fraction; FAC: right ventricular area change fraction; TAPSE: tricuspid annular systolic motion amplitude.

[0055] like Figure 8 As shown, 6 rats in the TR group were implanted with coronary stents. Cardiac ultrasound was performed at 4 and 8 weeks of follow-up, showing that there was no significant change in the left ventricular function of the rats at 4 and 8 weeks, while the right ventricular function decreased significantly.

[0056] Those skilled in the art should understand that the present invention is not limited to the above embodiments, and the above embodiments and descriptions are only for explaining the principles of the present invention. Without departing from the spirit and scope of the present invention, the present invention may have various changes and improvements, and these changes and improvements fall within the scope of the present invention to be protected. The scope of protection of the present invention is defined by the attached claims and their equivalents.

Claims

1. A system for constructing a transjugular rat tricuspid regurgitation model, characterized in that: include: Anesthesia supplies, incision forming supplies, stent delivery systems, coronary stent systems, balloon dilatation systems, echocardiography equipment, incision suturing supplies, postoperative care supplies, The incision making kit is used to make an incision of 1-2 cm in size on rats.

2. The system for constructing a transjugular rat tricuspid regurgitation model according to claim 1, characterized in that: in, The anesthetic supplies include anesthetics and anesthetic needles, the anesthetic is 1% sodium pentobarbital, The incision forming supplies include surgical scissors, forceps, disinfectant and sterile drapes. The incision suturing supplies include suture needles and sutures. The postoperative care supplies include glucose and sodium chloride injection and a rewarming blanket.

3. The system for constructing a transjugular rat tricuspid regurgitation model according to claim 2, characterized in that: in, The rats are adult rats, and the adult rats are 70-day-old rats.

4. The system for constructing a transjugular rat tricuspid regurgitation model according to claim 1, characterized in that: in, The stent delivery system includes a guide sheath assembly and a guide wire. The guide sheath assembly includes a guide sheath and an injection needle. The injection needle is removably arranged on the guide sheath. The guide wire is adapted to the guide sheath and is used to be guided into the rat heart through the guide sheath.

5. The system for constructing a transjugular rat tricuspid regurgitation model according to claim 4, characterized in that: in, The coronary stent system is a platinum-chromium alloy coronary stent system. The balloon dilatation system comprises a balloon and a balloon dilatation pressure pump.

6. The system for constructing a transjugular rat tricuspid regurgitation model according to claim 4, characterized in that: in, The diameter of the guide sheath is 0.075 mm, the diameter of the guide wire is 0.007 mm, and the outer diameter of the stent of the coronary stent system after release is 3.33 mm.

7. The system for constructing a transjugular rat tricuspid regurgitation model according to claim 1, characterized in that: Also includes: Shaving supplies, including razors.

8. Use of the system for constructing a transjugular rat tricuspid regurgitation model as described in any one of claims 1 to 6 in constructing a transjugular rat tricuspid regurgitation model.

9. The use according to claim 8, characterized in that: The following steps are involved: Step 1, using the anesthetic product to perform general anesthesia on the rat by intraperitoneal injection, then removing the hair on the neck and chest of the rat, and treating it with iodine disinfectant, and then covering the neck and chest area with a sterile drape to establish a sterile area for surgery; Step 2, using surgical scissors to make an incision on the right neck of the rat to expose the right jugular vein, then inserting the guide sheath assembly of the stent delivery system into the right jugular vein, pulling out the needle of the guide sheath assembly, leaving the guide sheath of the guide sheath assembly in the right jugular vein, then inserting the guide wire of the stent delivery system into the right heart through the guide sheath, and pulling out the guide sheath; Step 3, using an echocardiography device to take a thoracic echocardiogram of the rat, under the guidance of the transthoracic echocardiogram, the coronary stent system is delivered to the tricuspid valve ring along the guide wire, after confirming that the stent is located at the tricuspid valve, the balloon expansion pressure pump of the balloon expansion system is used to release the stent at a pressure of 15 kPa, and then the liquid in the balloon is released, the guide wire is completely withdrawn, and finally the puncture site is pressed for 3-5 minutes to stop bleeding and the incision is sutured with the incision suture supplies; Step 4, after surgery, the postoperative care products are used for fluid infusion and rewarming, and tricuspid valve regurgitation is detected by cardiac ultrasound 4 and 8 weeks after surgery, thereby obtaining a transjugular rat tricuspid valve regurgitation model.

10. The system for constructing a transjugular rat tricuspid regurgitation model according to claim 9, characterized in that: in, The tip of the guidewire is molded into a curled shape before introduction, thereby preventing the guidewire from entering the inferior vena cava.

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