CN116058992A - System and device for constructing near-end thoracic aortic aneurysm animal model - Google Patents
System and device for constructing near-end thoracic aortic aneurysm animal model Download PDFInfo
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Abstract
The invention discloses a construction system and a device of a near-end thoracic aortic aneurysm animal model, wherein the system comprises: a fixing unit; a first treatment unit that opens along the anterior midline of the neck and exposes to chest second intercostal levels; a second processing unit for separating thyroid and muscle in front of the trachea and pushing the thyroid and muscle to both sides; cutting the sternum down the anterior midline from the mid-point of the superior sternum fossa to a second intercostal level with exposed thymus leaves; a third processing unit for pulling the thymus leaf and sternum of the animal forward and upward to make the sternum of the animal angled relative to the face of the neck of the animal and expose the proximal thoracic aorta; a fourth treatment unit for dissecting fibrous connective tissue and adipose tissue around the proximal thoracic aorta to expose the proximal thoracic aorta; the incubation unit is used for placing a disinfection piece at the exposed proximal thoracic aorta, and placing an oncological incubation liquid into the disinfection piece for incubation; and a fifth processing unit for taking out the sterilizing element, flushing the sternum and neck incisions with flushing liquid, and obtaining the model.
Description
Technical Field
The invention belongs to the field of biology, and relates to an animal model, in particular to a system and a device for constructing a near-end thoracic aortic aneurysm animal model.
Background
The main characteristic of the aortic aneurysm is that compared with the normal aorta, the local permanent expansion of the aortic wall is more than or equal to 50%; aortic aneurysms are an increasingly high incidence of silent, life-threatening disease. Thoracic Aortic Aneurysms (TAA) account for 35% of all aortic aneurysms, with 6 to 10 per 10 tens of thousands of people per year reported to have a prevalence of 0.16% to 0.34%. However, the above data may be underestimated, as studies have shown that about 95% of cases are asymptomatic and not found until after TAA rupture, resulting in death. Over time, the size of the TAA tends to expand and as the diameter increases, the risk of breakage increases significantly (2% for TAA in the range of 4.0 to 4.9 cm; 7% for TAA >6.0 cm). TAA burst bleeding is fatal, but premature TAA preventative surgical repair can lead to more surgical complications and even perioperative death, and patients cannot benefit from TAA early intervention surgery. Most patients wait about 5 years before being advised by doctors to perform a surgical repair, and this long time window suggests that there is a need to develop conservative therapies such as drugs that can prevent or slow the expansion of TAA. However, there is no demonstration of effective inhibition or prevention of the relevant progression of TAA by drug therapy, mainly because TAA pathogenesis has not been studied intensively.
At present, the cognition of people on the pathogenesis of TAA mainly comes from an experimental TAA model, and the most widely applied mouse TAA model in TAA research is a descending aortic aneurysm constructed by exposing a descending aorta through left chest opening and then incubating with elastase or 0.5mol/L calcium chloride solution. Studies have shown that the germ layer sources of the proximal thoracic aorta (ascending aorta and aortic arch) are different from those of the descending aorta, which develops from neural crest cells, while the descending aorta develops from mesoderm, the sources of which are closely related to the pathogenesis of aneurysms. In addition, the near-end thoracic aortic valve has great differences in anatomy, histology and hemodynamic characteristics from the descending aorta, so that the prior scholars consider that the pathogenesis of the near-end thoracic aortic valve is different from that of the descending aortic valve, and the animal model of the descending aortic valve cannot simulate the pathophysiology of the near-end thoracic aortic valve. And clinically, cases of proximal thoracic aortic aneurysm (ascending aortic aneurysm and aortic aneurysm) account for more than 60% of cases of thoracic aortic aneurysm, we now need to develop an animal model of proximal thoracic aortic aneurysm to study its pathogenesis. Apoe knockout mice can be constructed with subcutaneous pumping of angiotensin to create an ascending aortic aneurysm, but recent studies indicate that such aneurysms often incorporate aortic dissection or wall-to-wall hematoma, which is clearly different from the pathophysiological changes of clinical TAA, which are pure aortic wall full-expansion. There is a foreign study on the construction of the ascending aortic aneurysm by exposing rat ascending aorta with elastase through a median thoracotomy operation of longitudinal split thoracotomy, but the operation requires trachea cannula, has high operation difficulty, and has large operation wound, easily causes pulmonary contusion and pulmonary complications, and has the death rate of animals as high as 19% (the death rate of constructing the descending aortic aneurysm by thoracotomy is as high as 35%). Therefore, we have urgent need to develop a minimally invasive proximal thoracic aortic aneurysm animal model to study its pathogenesis and screen drugs.
Disclosure of Invention
The present invention aims to solve at least one of the technical problems existing in the prior art. Therefore, the invention provides a system and a device for constructing a near-end thoracic aortic aneurysm animal model; the method for constructing the proximal thoracic aortic aneurysm model by exposing the proximal thoracic aortic incubation elastase through the median incision of the neck of the mouse can avoid median thoracic surgery and trachea cannula, and construct aneurysms positioned in the ascending aorta and aortic arch. The model constructed by the system has the situation that the thoracic aortic aneurysm breaks and dies, which is a clinically common situation that many models can not simulate at present, and the model in the invention lays a foundation for the pathophysiological mechanism research of the proximal thoracic aortic aneurysm in the future, and provides experimental technology and scheme for solving the related life science problems.
The application discloses a system for constructing a proximal thoracic aortic aneurysm animal model, comprising:
a fixing unit for fixing the animal to the surface of the operating table;
a first treatment unit that opens to a chest second intercostal level along the anterior midline of the animal's neck using a cutting element, exposing the chest second intercostal level;
the second treatment unit is used for separating thyroid and muscle in front of the animal trachea by adopting a separating piece and pushing the thyroid and the muscle to two sides; cutting the sternum down the anterior midline from the midpoint of the suprasternal fossa to a second intercostal level of the animal with a cutting element to expose thymus leaves;
a third processing unit, which adopts a first stripping piece to pull the thymus leaf and the sternum of the animal forward and upward, so that the sternum of the animal forms an angle relative to the surface of the neck of the animal, and the ascending aorta and the aortic arch of the neck are displayed;
a fourth treatment unit for stripping connective tissue and adipose tissue around the proximal thoracic aorta using a second stripping member to expose the proximal thoracic aorta;
an incubation unit for placing a disinfection piece at the exposed proximal thoracic aorta, and incubating for Nmin with an oncological incubation solution at the disinfection piece;
and a fifth processing unit, configured to take out the disinfecting piece, flush the operation area with a flushing liquid M times, and close the sternum and neck incisions to obtain the proximal thoracic aortic aneurysm animal model.
Optionally, the angle in the angle of the sternum and/or thymus leaf of the animal relative to the face of the neck of the animal is a, and the range of a is: a is more than 0 and less than or equal to 180 degrees; the range of a is preferably: a is more than or equal to 30 degrees and less than or equal to 45 degrees.
The angle between the top of the operating table and the horizontal plane is b, and the range of b is as follows: b is more than 0 and less than or equal to 180 degrees; b is preferably 180 degrees, i.e. the top of the operating table is parallel to the horizontal plane.
The incubation liquid comprises: elastase; the elastase is preferably porcine elastase; the volume of elastase is c, and the interval range of c is 10-30 mu L; preferably 15. Mu.L;
optionally, the range of N includes: the expansion can be obviously caused after 5-30min, and the effect of 10min is better than that of 5min.
The system further comprises: the positioning unit is used for positioning an operation area of the animal, and the operation area comprises a front midline of the neck of the animal; the positioning unit is positioned between the fixing unit and the first processing unit.
The system further comprises: and the disinfection unit is used for disinfecting the operation area of the animal and/or the area around the operation area.
The tumor forming position of the animal model is positioned at a proximal thoracic aortic segment, and the proximal thoracic aortic segment comprises an ascending aorta and an aortic arch;
optionally, the animal model is a mouse model;
alternatively, the animal is a mouse, which is a male 8-12 week old wild type C57BL mouse.
A device for constructing a proximal thoracic aortic aneurysm animal model, the device comprising: one or more processors, and memory for storing one or more computer programs that, when executed by the one or more processors, implement:
fixing the animal on the surface of an operating table;
opening along the anterior midline of the animal's neck to a thoracic second intercostal level with a cutting member exposing the thoracic second intercostal level;
separating thyroid gland and muscle in front of animal trachea by separating piece and pushing to two sides; cutting the sternum down the anterior midline from the midpoint of the suprasternal fossa to a second intercostal level of the animal with a cutting element to expose thymus leaves;
the thymus leaf and the sternum of the animal are pulled up forwards and upwards by adopting the first stripping piece, so that the sternum of the animal forms an angle relative to the surface of the neck of the animal, and the ascending aorta and the aortic arch of the neck are displayed;
stripping connective tissue and adipose tissue around the proximal thoracic aorta with a second stripping member to expose the proximal thoracic aorta;
placing a sterilizing piece at the exposed proximal thoracic aorta, and placing an oncological incubation liquid into the sterilizing piece for incubation for Nmin;
and taking out the sterilizing piece, flushing the operation area for M times by adopting flushing liquid, and closing the sternum and neck incisions to obtain the proximal thoracic aortic aneurysm animal model.
The device further comprises a first stripper member comprising a working portion that acts on tissue of the animal; the working part comprises a draw hook and a first supporting section which are connected, and an angle is formed between the surface of the draw hook and the surface of the first supporting section; the included angle between the surface of the drag hook and the surface of the first supporting section is d, and the range of d is 10-90 degrees;
optionally, the drag hook is arranged as a drag hook plate connected with the first supporting section or a drag hook ring composed of a rod-shaped object; the first support section is arranged as a support plate or a support rod.
The apparatus further comprises: a cutting member, a separating member, a second peeling member; the cutting member includes: a pair of scissors; the separator includes: separating pliers; the second peeling member includes: microsurgery forceps and microsurgery forceps.
The application has the following beneficial effects:
1. the application innovatively discloses a system for constructing a proximal thoracic aortic aneurysm animal model, which exposes a proximal thoracic aortic artery through a front-neck median incision approach and incudes elastase, so that a new proximal thoracic aortic aneurysm mouse in-vivo model is established; the model helps to study pathogenesis and treatment strategies of proximal thoracic aortic aneurysm formation. And the system produces repeatable, robust aortic dilation in the ascending aorta and aortic arch; experimental proximal thoracic aortic aneurysm models are less technically challenging to build and less invasive to create.
2. The method for constructing the proximal thoracic aortic aneurysm model by exposing the proximal thoracic aortic aneurysm elastase through the median incision of the neck of the mouse creatively can avoid longitudinal thoracic bone cleavage operation and trachea cannula, construct aneurysms positioned on the proximal thoracic aortic artery, retain most of sternum integrity, improve postoperative respiratory function, relieve postoperative pain, and enable the postoperative recovery of the mouse to be faster, so that the death rate is greatly reduced. The model constructed by the system can better simulate the pathophysiological change of the full-layer expansion of the pure aortic wall of the clinical TAA. In addition, the model has the condition of fracture and death of the thoracic aortic aneurysm, which is a clinically common situation that many models can not simulate at present, and the model provides a better experimental technology and scheme for the pathophysiological mechanism research of the proximal thoracic aortic aneurysm in the future.
3. The application innovatively discloses a device comprising a near-end thoracic aortic aneurysm animal model construction system, wherein the system can be placed in the device to form a clinical automatic processing station, so that the standardization and automation of model construction are ensured; meanwhile, the device also discloses specific structures such as a first stripping piece, a cutting piece, a separating piece, a second stripping piece and the like in the system, wherein the first stripping piece can realize the pulling effect on animal tissues through the angle arrangement between the drag hook and the first supporting section.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings required for the description of the embodiments will be briefly described below, and it is apparent that the drawings in the following description are only some embodiments of the present invention, and other drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.
FIG. 1 is a schematic flow chart of a system for constructing a proximal thoracic aortic aneurysm animal model according to an embodiment of the present invention;
FIG. 2 is a schematic illustration of a first stripper member and a model construction procedure for inducing a thoracic aortic aneurysm through an anterior cervical midline incision provided in accordance with an embodiment of the present invention;
FIG. 3 is a schematic view of a proximal thoracic aortic aneurysm according to an embodiment of the present invention;
FIG. 4 is a representative ultrasound image, morphology and expansion statistics of a proximal thoracic aortic aneurysm model provided by an embodiment of the present invention;
FIG. 5 is a schematic view of a first stripper member provided in accordance with an embodiment of the present invention and including only a first support section (the drag hook is a drag hook ring and the first support section is a support bar);
FIG. 6 is a schematic view of a first stripper member comprising a first support section (the drag hook is a drag hook ring, the first support section is a support bar) and a handle (the handle is a support sheet) according to an embodiment of the present invention;
FIG. 7 is a schematic view of the overall structure of a first stripper member comprising a first support section (the drag hook is a drag hook ring, the first support section is a support rod) and a handle portion (the handle portion is a mouth shape with an opening) provided in an embodiment of the present invention;
FIG. 8 is a schematic diagram of a front view of a first stripper member comprising a first support section (the drag hook is a drag hook ring, the first support section is a support bar) and a handle portion (the handle portion is a die with an opening) provided in an embodiment of the present invention;
FIG. 9 is a schematic side view of a first stripper member comprising a first support section (the drag hook is a drag hook ring, the first support section is a support bar) and a handle portion (the handle portion is a die with an opening) provided in accordance with an embodiment of the present invention;
FIG. 10 is a schematic top view of a first stripper member comprising a first support section (the drag hook is a drag hook ring, the first support section is a support bar) and a handle portion (the handle portion is a die with an opening) according to an embodiment of the present invention;
FIG. 11 is a schematic view of the overall structure of a first stripper member comprising a first support section (the drag hook is a drag hook ring, the first support section is a support plate) and a handle (the handle is a support bar) according to an embodiment of the present invention;
fig. 12 is a schematic view of the overall structure of a first stripper member including a first supporting section (the drag hook is a drag hook plate, the first supporting section is a supporting plate) and a handle (the handle is a supporting rod) according to an embodiment of the present invention.
Detailed Description
In order to enable those skilled in the art to better understand the present invention, the following description will make clear and complete descriptions of the technical solutions according to the embodiments of the present invention with reference to the accompanying drawings.
In some of the flows described in the specification and claims of the present invention and in the foregoing figures, a plurality of operations occurring in a particular order are included, but it should be understood that the operations may be performed out of order or performed in parallel, with the order of operations such as 101, 102, etc., being merely used to distinguish between the various operations, the order of the operations themselves not representing any order of execution. In addition, the flows may include more or fewer operations, and the operations may be performed sequentially or in parallel. It should be noted that, the descriptions of "first" and "second" herein are used to distinguish between different messages, devices, modules, etc., and do not represent a sequence, and are not limited to the "first" and "second" being different types.
The following description of the embodiments of the present invention will be made clearly and completely with reference to the accompanying drawings, in which it is apparent that the embodiments described are only some embodiments of the present invention, but not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments according to the invention without any creative effort, are within the protection scope of the invention.
Fig. 1 is a schematic flow chart of a system for constructing a proximal thoracic aortic aneurysm animal model according to an embodiment of the present invention, specifically, the system includes:
a fixing unit 101 for fixing an animal to a top of an operating table; the table top of the operating table can be the operating table top of a Zeiss Stemi305 stereoscopic microscope;
a first treatment unit 102 that opens (cuts the skin) along the anterior midline of the animal's neck to a thoracic second intercostal level using a cutting element, exposing the thoracic second intercostal level;
a second processing unit 103 for separating thyroid and muscle in front of the animal trachea by using a separating member and pushing the thyroid and muscle to two sides; cutting the sternum down the anterior midline from the midpoint of the superior sternal fossa to a second intercostal level with a cutting element to expose thymus leaves; cutting the sternum to a depth of greater than 2mm, preferably 5mm, of a second rib of the animal with a cutting element;
a third processing unit 104, which adopts a first stripper to pull the thymus leaf and the sternum of the animal together to the front upper side, so that the sternum of the animal forms an angle relative to the surface of the neck of the animal, and the ascending aorta and the aortic arch of the neck are displayed; here, when the thymus leaf and the sternum are pulled up, the right innominate artery and the left common carotid artery are exposed by slightly dissociating, and the pulsating aortic arch and the ascending aorta (proximal thoracic aorta) can be seen by dissociating along the two arteries down to the proximal end thereof;
a fourth processing unit 105 for peeling connective tissue and adipose tissue around the proximal thoracic aorta (ascending aorta and aortic arch) using a second peeling member, sufficiently exposing the proximal thoracic aorta; before the aortic arch lesser curvature side is stripped, fully freeing adipose tissues and fibrous connective tissues on the aortic arch lesser curvature side as much as possible, and then downwards freeing the lesser curvature side along a gap between the aortic arch and a fibrous membrane on the great curvature side so as to avoid the death of mice due to pleural rupture pneumothorax; when the second stripping piece is used for stripping, the attention is needed to avoid damaging the proximal thoracic aorta and pleura;
an incubation unit 106, configured to place a sterilizing element at the exposed proximal thoracic aorta, and incubate Nmin with an oncological incubation solution placed in the sterilizing element; the sterilizing piece is clean sterilized cotton; or the disinfection piece is disinfection cotton carrying the tumorigenic incubation liquid, and the tumorigenic incubation liquid is not required to be additionally placed in the disinfection cotton; the area of the sterilized cotton is about 6X 3X 1mm.
A fifth processing unit 107 for taking out the sterilizing element, flushing the operation area M times with a flushing liquid, closing (suturing) the sternum and neck incisions, and obtaining a proximal thoracic aortic aneurysm animal model after 14-28 days.
In one example, 8-12 week old adult wild type male C57BL/6J mice were anesthetized with 2% tribromoethanol (350 mg/kg) intraperitoneally. Removing hair on neck and chest of the mouse with depilatory cream, and fixing the mouse in supine position on the operating table surface under the body vision mirror; the operator is located on the head side of the animal.
In one embodiment, the angle in the plane of the sternum of the animal relative to the neck of the animal is a, the range of a being: a is more than 0 and less than or equal to 180 degrees; the range of a is preferably: a is more than or equal to 30 degrees and less than or equal to 45 degrees.
In one embodiment, the operating table has an angle between the top of the operating table and a horizontal plane, the angle being b, b ranging from: b is more than 0 and less than or equal to 180 degrees; b is preferably 180 degrees, i.e. the top of the operating table is parallel to the horizontal plane.
In one embodiment, the incubation liquid comprises: elastase; the elastase is preferably porcine elastase; the volume of elastase is c, and the interval range of c is 10-30 mu L; preferably 15. Mu.L. Since elastase digestion varies from vial to vial, the appropriate volume and time of administration should be determined prior to the formal procedure to ensure adequate digestion to maximize distension while avoiding over-digestion of elastase, resulting in intraoperative bleeding or premature rupture.
In one embodiment, the range of N includes: 5-30min; in this example 5min and 10min; the obvious expansion can be caused after 5min, and the effect is better than 5min after 10 min.
In one embodiment, the tumorigenic incubation fluid further comprises 0.9% physiological saline; a total of 29 mice underwent surgery (9 saline groups, 95 min elastase groups and 11 10min elastase groups). The operating time (except for elastase or saline incubation time) of the mice was 16.89±0.47 min (mean±standard error). Two mice of the 10min incubation group died from the thoracic aortic aneurysm rupture on postoperative day 7 and day 18. In the last ultrasound examination, their thoracic aortic aneurysms reached maximum diameters of 2.78mm and 2.01mm, respectively. The use of elastase around the outer membrane of the proximal thoracic aorta resulted in significant aortic dilation compared to saline incubation, as shown in figures 4A-D; as shown in fig. 4E, the proximal thoracic aortic expansion rate (mean ± standard error) was significantly higher for both the 10min elastase incubation group (n=10, 71.44% ± 10.45%) and the 5min incubation group (n=9, 42.67% ± 3.72%) than for the saline incubation group (n= 9,7.37% ± 0.94%, P < 0.001). Elastase incubation for 10min resulted in more pronounced proximal thoracic aortic dilation than 5min (fig. 2e, p < 0.05). The mean proximal thoracic aortic size was 1.43 mm.+ -. 0.02mm for the saline group, 2.01 mm.+ -. 0.05mm for the 5min elastase incubation group, and 2.37 mm.+ -. 0.15mm for the 10min group. To show the trend of aortic expansion over time, figure 2F summarizes aortic diameter data from pre-and post-operative weekly ultrasound-examined mice. In the 5-minute application group, the maximum aortic expansion occurred at day 7 post-surgery (42.23% ± 3.92%) and a slight retraction trend of aortic expansion was observed at day 28 (36.94% ± 5.30%). In the 10min application group, the maximum aortic dilation occurred at day 14 post-surgery (80.36% ± 15.97%), and a slight trend of aortic reduction was also observed at day 28 (75.71% ± 15.73%).
In addition, the results of the histopathological examination showed that the luminal and adventitial thickness of the Proximal Thoracic Aortic Aneurysm (PTAA) was significantly greater than that of the normal saline-incubated aorta (control). The aortic wall thickness and cross-sectional area of PTAA were significantly higher than the control. Elastin fiber from PTAA was degraded as shown by elastotic vangieson staining, but in the aorta of the control group, elastin fiber was well-aligned and dense. Immunohistochemical staining of smooth muscle cells with ACTA2 showed a significant increase in the ACTA2 negative area in PTAA, indicating that PTAA had a loss of smooth muscle cells. By immunostaining the blood vessels with vascular endothelial-cadherin, a significant increase in neovascular blood vessels was observed in the PTAA adventitia.
The test results of the apoptotic and proliferative capacity of smooth muscle cells in PTAA indicate that: apoptotic smooth muscle cells were present in PTAA, whereas no apoptotic smooth muscle cells were found in the control group, and SMCs with proliferative activity were present only in PTAA tissue.
Quantitative RT-qPCR analysis showed that several pro-inflammatory markers in PTAA tissue, including tumor necrosisfactor- α, interleukin-1β, and Andinterleukin-6, were significantly increased. Likewise, the mRNA levels of Col1a1, col3a1, mp2 and mp9 were also significantly increased. immunoWestern blotting results show that protein levels of type III collagen, type I collagen, MMP2 and MMP9 in PTAA lesions are also up-regulated, quantitative gray level analysis shows that the protein levels of the genes are statistically significantly increased except for type I collagen, which only shows an increasing trend, indicating that collagen synthesis in PTAA tissues is up-regulated and extracellular matrix degradation is enhanced. Immunofluorescence results showed that collagen III, collagen I, MMP and MMP9 were located in the gap between the outer membrane and the elastic plate of PTAA lesions. In the control group, collagen III, MMP2 and MMP9 were mainly located in the aortic middle layer, while collagen I was mainly located in the adventitia.
Macrophages and CD4 positive T cells predominate in aortic aneurysm inflammation, play an important role in aneurysm formation and development, being the primary inflammatory cells in aneurysm lesions. Immunohistochemical staining of the aortic wall for CD68 (biomarker of macrophages) and CD4 (biomarker of CD4 positive T cells) found that significantly increased infiltration of CD68 positive macrophages and cd4+ T cells was observed in PTAA lesions, as compared to control, mainly in the adventitia of tumor wall tissue.
The above experiments show that the incubation of elastase by exposing the proximal thoracic aorta through the small anterior cervical incision can lead to significant expansion of the proximal thoracic aorta and PTAA, and the molecular pathology experiment results prove that the model pathological changes conform to the basic pathological characteristics of aortic aneurysm.
The system further comprises: the positioning unit is used for positioning an operation area of the animal, and the operation area comprises a front midline of the neck of the animal; the positioning unit is positioned between the fixing unit and the first processing unit.
The system further comprises: and the disinfection unit is used for disinfecting the operation area of the animal and/or the area around the operation area. The disinfection mode is directly used for disinfection in the prior art.
In one embodiment, the system further comprises: a post-operation treatment unit for feeding normal feed and sterile water to the mice for 28 days; alternatively, a small amount of 5% lidocaine cream was applied to the surgical wound to reduce pain in the mice after closing the sternal and cervical cuts prior to feeding. The mice were allowed to recover for several minutes on the blanket and, after full wake-up, were then subjected to the post-operative treatment unit procedure.
The tumorigenic position of the animal model is positioned at the proximal thoracic aortic segment; the proximal thoracic aorta includes the ascending aorta and the aortic arch; optionally, the animal model is a mouse model; alternatively, the animal is a mouse, which is a wild-type mouse of 8-12 weeks of age.
In one embodiment, all animal protocols are reviewed and approved by the animal care and use committee of the experimental animal center of the national center for cardiovascular disease, fungium, national center for cardiovascular disease.
A device for constructing a proximal thoracic aortic aneurysm animal model, the device comprising: one or more processors, and memory for storing one or more computer programs that, when executed by the one or more processors, perform the following methods:
fixing the animal on the surface of an operating table;
opening along the anterior midline of the animal's neck to a thoracic second intercostal level with a cutting member exposing the thoracic second intercostal level;
separating thyroid gland and muscle in front of animal trachea by separating piece and pushing to two sides; cutting the sternum down the anterior midline from the midpoint of the suprasternal fossa to a second intercostal level of the animal with a cutting element to expose thymus leaves;
the thymus leaf and the sternum of the animal are pulled up forwards and upwards by adopting the first stripping piece, so that the sternum of the animal forms an angle relative to the surface of the neck of the animal, and the ascending aorta and the aortic arch of the neck are displayed;
stripping connective tissue and adipose tissue around the proximal thoracic aorta with a second stripping member to expose the proximal thoracic aorta;
placing a sterilizing piece at the exposed proximal thoracic aorta, and placing an oncological incubation liquid into the sterilizing piece for incubation for Nmin;
and taking out the sterilizing piece, flushing the operation area for M times by adopting flushing liquid, and closing the sternum and neck incisions to obtain the proximal thoracic aortic aneurysm animal model.
In one embodiment, the device further comprises a first stripper member comprising a working portion that acts on the tissue of the animal; the working part comprises a draw hook and a first supporting section which are connected, and an angle is formed between the surface of the draw hook and the surface of the first supporting section; the included angle between the surface of the drag hook and the surface of the first supporting section is d, and the range of d is 10-90 degrees; d preferably ranges from 30 degrees to 45 degrees;
optionally, the drag hook is arranged as a drag hook board 5 connected with the first supporting section or a drag hook ring 1 composed of a rod-shaped object; the first support section is provided as a support plate 4 or support bar 2.
In one embodiment, the outer surface of the first stripping member is rounded, so that the animal tissue is not damaged, and no accidental injury is caused to an operator.
In one embodiment, the apparatus further comprises: a cutting member, a separating member, a second peeling member; the cutting member includes: a pair of scissors; the separator includes: the separating forceps are preferably blunt separating forceps; the second peeling member includes: microsurgery forceps and microsurgery forceps.
Fig. 2 is a front view of a first stripper member and a model building procedure for inducing a thoracic aortic aneurysm through an anterior cervical midline incision, according to an embodiment of the present invention. Side view of the first stripper member. (C) The skin is opened and the thyroid and anterior muscle of the trachea are pushed to both sides. Sternum is cut to a second intercostal level. (E) The sternum is lifted 30 to 45 degrees anteriorly and superior, further free posteriorly, exposing the target aorta. Left cervical total represents the left common carotid artery and right innominate represents the right innominate artery. (F) Proximal thoracic aortic incubations were performed using elastase or saline soaked sterile cotton. And (G) taking out sterilized cotton (elastase incubation group).
FIG. 3 is a schematic view of a proximal thoracic aortic aneurysm according to an embodiment of the present invention; wherein a represents an aortic arch aneurysm, b represents an ascending aortic aneurysm, and a and b constitute a proximal thoracic aortic aneurysm; c represents the descending aorta; d represents the diaphragm.
Fig. 4 is an ultrasound image, morphology and expansion ratio of a Proximal Thoracic Aortic Aneurysm (PTAA) model provided by an embodiment of the present invention, wherein, (a). Representative ultrasound image of PTAA (5 min elastase application), the maximum ascending aortic diameter 28 days after surgery is 2.25mm. (B) Control representative ultrasound image of thoracic aorta, maximum ascending diameter of 1.38mm 28 days post-operation. Typical morphology of PTAA. (D) control typical morphology of thoracic aorta. (E) Proximal thoracic aortic expansion ratio of the post-operative 14 day incubation group with elastase and physiological saline at 5min, 10 min. The statistical test method comprises the following steps: mann-Whitney test, P <0.05, P <0.001. (F) Changes in proximal thoracic aortic expansion rate over time during PTAA formation. Over time, mice were exposed to elastase for 5 minutes (n=9) or 10 minutes (n=9) or to the maximum ascending aortic diameter (mean ± s.e.m.) of the 10 minute saline group (n=9). Comparing the proximal thoracic aortic expansion ratio of the 5-min or 10-min elastase incubation group with the physiological saline incubation group, respectively, P <0.01, P <0.001.
Fig. 5 to fig. 12 are schematic structural views of a first stripping member provided by the embodiment of the present invention, where, as shown in fig. 5 to fig. 10, a first supporting section includes supporting rods 2 disposed at two ends of a drag hook, the drag hook is a drag hook ring 1, two ends of the drag hook ring 1 are integrally connected with one end of the supporting rod 2, or the connection mode between the drag hook ring 1 and one end of the supporting rod 2 may be also movable connection, i.e. the included angle d may be adjusted as required; as shown in fig. 2E and 9, the drag hook ring 1 is connected with the supporting rod 2 through hooks, the length of the hooks is not limited, and the hooks are arranged to pull up tissues on the premise of not damaging the muscle tissues. The mode that the drag hook ring 1 and one end of the supporting rod 2 are movably connected is not shown in the drawing, one ends of the drag hook ring 1 and the supporting rod 2 are specifically connected through a rotating shaft, or a locking piece is arranged at the rotating shaft, so that relative rotation between the drag hook ring 1 and the supporting rod 2 can not occur when no external force is applied. As shown in fig. 11 and 12, the first support section comprises a support plate 4 connected with a draw hook, the draw hook is arranged as a draw hook plate 5 or a draw hook ring 1, one end of the draw hook plate 5 or the draw hook ring 1 is integrally connected with one end of the support plate 4, or the connection mode of the draw hook plate 5 or the draw hook ring 1 and one end of the support plate 4 can be movably connected, namely, the included angle d can be adjusted according to the requirement; the mode that the hook plate 5 or the hook ring 1 is movably connected with one end of the supporting rod 2 is not shown in the drawing, and the hook plate 5 or the hook ring 1 is connected with one end of the supporting rod 2 through a rotating shaft, or a locking piece is arranged at the rotating shaft, so that relative rotation between the hook plate 5 or the hook ring 1 and the supporting plate 4 can not occur when no external force is applied.
In one embodiment, the first stripper member further comprises a handle portion connected to the working portion, the handle portion being connected to the first support section; the surface of the handle part and the surface of the first support section are positioned on the same plane or are arranged at an angle; the handle is provided in, but not limited to, the following manner, which may also be other shapes or manners that facilitate handling; as shown in fig. 5, the handle is provided with a supporting rod 2 integrally connected with the first supporting section, and the surface of the handle is in the same plane with the surface of the first supporting section; as shown in fig. 6, the handle is provided with a supporting piece 3 integrally connected with the first supporting section, the surface of the supporting piece 3 is provided with a finger-shaped groove convenient for hand pinching, and the surface of the handle is in the same plane with the surface of the first supporting section; as shown in fig. 7, 8, 9, 10, the handle is provided in a mouth shape having an opening.
The results of the verification of the present verification embodiment show that assigning an inherent weight to an indication may moderately improve the performance of the present method relative to the default settings.
It will be clear to those skilled in the art that, for convenience and brevity of description, specific working procedures of the above-described systems, apparatuses and units may refer to corresponding procedures in the foregoing method embodiments, which are not repeated herein.
In the several embodiments provided in this application, it should be understood that the disclosed systems, apparatuses, and methods may be implemented in other ways. For example, the apparatus embodiments described above are merely illustrative, e.g., the division of the units is merely a logical function division, and there may be additional divisions when actually implemented, e.g., multiple units or components may be combined or integrated into another system, or some features may be omitted or not performed.
The units described as separate parts may or may not be physically separate, and parts displayed as units may or may not be physical units, may be located in one place, or may be distributed on a plurality of units. Some or all of the units may be selected according to actual needs to achieve the purpose of the solution of this embodiment.
In addition, each functional unit in the embodiments of the present invention may be integrated in one processing unit, or each unit may exist alone physically, or two or more units may be integrated in one unit. The integrated units may be implemented in hardware or in software functional units.
While the foregoing describes a construction apparatus provided by the present invention in detail, those skilled in the art will recognize that there are variations to the present invention in terms of specific embodiments and application ranges according to the concepts of the embodiments of the present invention, and the present disclosure should not be construed as limited to the foregoing description.
Claims (10)
1. A system for constructing a proximal thoracic aortic aneurysm animal model, comprising:
a fixing unit for fixing the animal to the surface of the operating table;
a first treatment unit that opens to a chest second intercostal level along the anterior midline of the animal's neck using a cutting element, exposing the chest second intercostal level;
the second treatment unit is used for separating thyroid and muscle in front of the animal trachea by adopting a separating piece and pushing the thyroid and the muscle to two sides; cutting the sternum down the anterior midline from the midpoint of the suprasternal fossa to a second intercostal level of the animal with a cutting element to expose thymus leaves;
a third processing unit, which adopts a first stripping piece to pull the thymus leaf and the sternum of the animal forward and upward, so that the sternum of the animal forms an angle relative to the surface of the neck of the animal, and the ascending aorta and the aortic arch of the neck are displayed;
a fourth treatment unit for stripping connective tissue and adipose tissue around the proximal thoracic aorta using a second stripping member to expose the proximal thoracic aorta;
an incubation unit for placing a disinfection piece at the exposed proximal thoracic aorta, and incubating for Nmin with an oncological incubation solution at the disinfection piece;
and a fifth processing unit, configured to take out the disinfecting piece, flush the operation area with a flushing liquid M times, and close the sternum and neck incisions to obtain a proximal thoracic aortic aneurysm animal model.
2. The system for constructing a model of a proximal thoracic aortic aneurysm according to claim 1, wherein the angle in the plane of the sternum of the animal relative to the neck of the animal is a, the range of a being: a is more than 0 and less than or equal to 180 degrees; the range of a is preferably: a is more than or equal to 30 degrees and less than or equal to 45 degrees.
3. The system for constructing a model of a proximal thoracic aortic aneurysm according to claim 1, wherein the operating table is angled between its top surface and a horizontal plane, the angle being b, b ranging from: b is more than 0 and less than or equal to 180 degrees; b is preferably 180 degrees, i.e. the top of the operating table is parallel to the horizontal plane.
4. The system for constructing a model of a proximal thoracic aortic aneurysm according to claim 1, wherein said incubation liquid comprises: elastase; the elastase is preferably porcine elastase; the volume of elastase is c, and the interval range of c is 10-30 mu L;
optionally, the range of N includes: 5-30min.
5. The system for constructing a model of a proximal thoracic aortic aneurysm according to any one of claims 1 to 4, wherein the system further comprises: the positioning unit is used for positioning an operation area of the animal, and the operation area comprises a front midline of the neck of the animal; the positioning unit is positioned between the fixing unit and the first processing unit.
6. The system for constructing a model of a proximal thoracic aortic aneurysm according to any one of claims 1 to 4, wherein the system further comprises: and the disinfection unit is used for disinfecting the operation area of the animal and/or the area around the operation area.
7. The system for constructing a proximal thoracic aortic aneurysm animal model according to any one of claims 1 to 4, wherein the tumorigenic site of the animal model is located in a proximal thoracic aortic artery, the proximal thoracic aortic artery including an ascending aortic artery and an aortic arch;
optionally, the animal model is a mouse model;
alternatively, the animal is a mouse, which is a wild-type mouse of 8-12 weeks of age.
8. A device for constructing a proximal thoracic aortic aneurysm animal model, the device comprising: one or more processors, and memory for storing one or more computer programs that, when executed by the one or more processors, implement:
fixing the animal on the surface of an operating table;
opening along the anterior midline of the animal's neck to a thoracic second intercostal level with a cutting member exposing the thoracic second intercostal level;
separating thyroid gland and muscle in front of animal trachea by separating piece and pushing to two sides; cutting the sternum down the anterior midline from the midpoint of the suprasternal fossa to a second intercostal level of the animal with a cutting element to expose thymus leaves; the thymus leaf and the sternum of the animal are pulled up forwards and upwards by adopting the first stripping piece, so that the sternum of the animal forms an angle relative to the surface of the neck of the animal, and the ascending aorta and the aortic arch of the neck are displayed;
stripping connective tissue and adipose tissue around the proximal thoracic aorta with a second stripping member to expose the proximal thoracic aorta;
placing a sterilizing piece at the exposed proximal thoracic aorta, and placing an oncological incubation liquid into the sterilizing piece for incubation for Nmin;
and taking out the sterilizing piece, flushing the operation area for M times by adopting flushing liquid, and closing the sternum and neck incisions to obtain the proximal thoracic aortic aneurysm animal model.
9. The apparatus for constructing a model of a proximal thoracic aortic aneurysm according to claim 8, wherein said apparatus further comprises a first stripper member, said first stripper member comprising a working portion, said working portion acting on tissue of said animal; the working part comprises a draw hook and a first supporting section which are connected, and an angle is formed between the surface of the draw hook and the surface of the first supporting section; the included angle between the surface of the drag hook and the surface of the first supporting section is d, and the range of d is 10-90 degrees;
optionally, the drag hook is arranged as a drag hook plate connected with the first supporting section or a drag hook ring composed of a rod-shaped object; the first support section is arranged as a support plate or a support rod.
10. The apparatus for constructing a model of a proximal thoracic aortic aneurysm according to claim 8, wherein said apparatus further comprises: a cutting member, a separating member, a second peeling member;
the cutting member includes: a pair of scissors;
the separator includes: separating pliers;
the second peeling member includes: microsurgery forceps and microsurgery forceps.
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| CN113545878A (en) * | 2021-07-20 | 2021-10-26 | 川北医学院 | Rat infrarenal abdominal aortic aneurysm model established through retroperitoneal approach and establishment method |
| CN114304053A (en) * | 2021-12-10 | 2022-04-12 | 广东金石医疗科技服务有限公司 | Construction method of rabbit aneurysm model |
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