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Establishing method of rat atrial fibrillation model for simulating characteristics of human diseases

A model and disease technology, applied in the medical field, can solve problems such as many animal ethics problems, high technical threshold, cardiac pacemaker pacing wires and expensive consumables for pulse generators, etc., and achieve the effect of simple and convenient establishment method

Pending Publication Date: 2019-11-22
ZHONGSHAN HOSPITAL FUDAN UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Currently available animal models of atrial fibrillation are divided into two types: one is the atrial fibrillation model induced by atrial overspeed pacing in experimental dogs, but this model needs to be established by experimental dogs, and the experimental dogs themselves have high cost of purchasing experimental animals and the difficulty of making models. It is cumbersome and costly, because the pacemaker implantation in experimental dogs needs to rely on digital subtraction angiography technology, and requires the cooperation of relevant professional and technical personnel. The required pacemakers, including pacing wires and pulse generators, are expensive consumables ; At the same time, there are many animal ethical issues in the experimental dog model, and it is difficult to carry out large-scale experimental research due to large-scale animal experiments; the types of experimental reagents (mainly various antibodies used in molecular biology research) that can be used for dogs are limited, etc. , these problems limit the application of this model of atrial fibrillation; in addition, the model is different from the characteristics of atrial fibrillation in real clinical situations
The other is a spontaneous atrial fibrillation model caused by the knockout of potassium ion channels in the mouse heart, but this model needs to knock out the target gene through CRISPA cas9 or other gene manipulation techniques. This gene editing technology has a higher threshold and is more expensive , involves tedious work such as breeding, multiplication, and conservation. In addition, the gene knockout model of atrial fibrillation can only replicate the atrial fibrillation caused by human gene defects, but cannot simulate most clinical atrial fibrillation cases

Method used

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  • Establishing method of rat atrial fibrillation model for simulating characteristics of human diseases
  • Establishing method of rat atrial fibrillation model for simulating characteristics of human diseases
  • Establishing method of rat atrial fibrillation model for simulating characteristics of human diseases

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] Embodiment 1 Construction of aortic coarctation model mouse

[0032] 40-week-old SD rats (20 in total) were randomly divided into a sham operation group and a coarctation of the aorta (TAC) group, with 10 rats in each group. The method of cervical aortic arch constriction (TAC) is as follows: rats are anesthetized by intraperitoneal injection of 1% amobarbital, the skin of the neck is depilated, an incision is made through the neck to the level of the manubrium of the rat, and the muscles are separated layer by layer. and fascia, bilateral carotid arteries can be seen after fully exposing the trachea, continue to separate along the left carotid artery and expose the aortic arch, and three branch vessels (brachiocephalic trunk, left common carotid artery, left subclavian artery) can be seen, of which the brachiocephalic artery The portion of the aortic arch between the trunk and the left common carotid artery is the target site for surgical narrowing. The 18G needle was...

Embodiment 2

[0033]Example 2 Detection of atrial remodeling in TAC model mice

[0034] For the TAC model mice obtained in Example 1, continue to feed for 1 week, conduct small animal ultrasound (vevo2100 ultrasound imaging system) detection, measure the blood flow velocity at the constriction of the aortic arch of the rat, continue to raise until after the TAC operation for 8 weeks, detect the inner diameter of the atrium, And the glucose metabolism level of rat atrial myocardium was detected by PET. According to the change of the inner diameter of the atrium and the change of the glucose metabolism level of the atrial muscle, the occurrence of cardiac remodeling was evaluated.

[0035] Ultrasound detection was performed 1 week after TAC, and the two-dimensional ultrasound images of the aortic arch in the coarctation group (TAC group) showed obvious stenosis; color Doppler ultrasound showed a significant increase in blood flow velocity at the stenosis, see figure 1 (The first column and t...

Embodiment 3

[0037] The establishment of embodiment 3 mouse atrial fibrillation model

[0038] It is confirmed by Example 2 that after the atrial enlargement of the TAC model mice occurs, that is, cardiac remodeling, further transesophageal electrical stimulation is performed to induce atrial fibrillation. The specific operation is as follows: the limbs of the rats are connected to the limb lead electrodes of the electrocardiogram, and the electrocardiogram is recorded. Connect the tail end of the 6F bipolar pacing wire to the electric stimulator, insert the head end into the esophagus of the rat through the mouth, the insertion depth is about 6-7cm, and the electric stimulation parameters are: voltage 40-50V, pulse frequency 20Hz, pulse width 4 ms, continuous stimulation for 30 s, and at the same time record the surface electrocardiogram of the experimental mice with a bioelectrical signal recorder.

[0039] Each experimental mouse was repeated 10 times for transesophageal electrical sti...

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Abstract

The invention discloses an establishing method of a rat atrial fibrillation model for simulating characteristics of human diseases. The establishing method comprises the steps that 1) an experimentalrat is raised to 35-45 weeks; 2) for the experimental rat, overload of the rat heart pressure is induced by cervical transverse aortic constriction, and a TAC model rat is formed; 3) after the transverse aortic constriction is carried out on the TAC model rat for 1-2 weeks, small animal ultrasonic treatment is conducted to detect a two-dimensional ultrasonic image and color Doppler flow image of blood vessels of a constriction part; 4) after the TAC model rat is constructed for 6-9 weeks, the inner diameter of the left atrium is detected through small animal ultrasonic treatment, the myocardial metabolism is detected by adopting PET, and the occurrence of atrial remodeling is verified; 5) after the transverse aortic constriction is carried out on the TAC model rat for 6-9 weeks, atrial fibrillation is induced through esophageal electrostimulation, a bioelectrical signal recorder is used for recording an electrocardiogram of the experimental rat body surface, and the rat atrial fibrillation model is obtained through verification. The constructed rat atrial fibrillation model can reflect the characteristics of the clinical human diseases, and the establishing method is simpler, moreconvenient, more economical and more efficient.

Description

technical field [0001] The invention belongs to the medical field, and relates to a method for establishing a mouse atrial fibrillation model, in particular to a method for establishing a mouse atrial fibrillation model for simulating the characteristics of human diseases. Background technique [0002] The specific mechanism of atrial fibrillation (AF) is not yet clear, in order to study atrial fibrillation, it is necessary to have a suitable animal model of atrial fibrillation. Currently available animal models of atrial fibrillation are divided into two types: one is the atrial fibrillation model induced by atrial overspeed pacing in experimental dogs, but this model needs to be established by experimental dogs, and the experimental dogs themselves have high cost of purchasing experimental animals and the difficulty of making models. It is cumbersome and costly, because the pacemaker implantation in experimental dogs needs to rely on digital subtraction angiography technol...

Claims

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Application Information

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IPC IPC(8): A01K67/02
CPCA01K67/02
Inventor 禹子清宿燕岗葛均波
Owner ZHONGSHAN HOSPITAL FUDAN UNIV
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