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Construction method of rapid heart failure model of type 2 diabetes mellitus mouse

A type 2 diabetes and construction method technology, which is applied in the field of rapid heart failure model construction in type 2 diabetes mice, can solve the problems of large individual differences in the degree of pathological changes, long modeling time, low modeling rate, etc., and achieve pathological changes The effect of high consistency, shortened heart failure time, and high molding rate

Active Publication Date: 2021-08-06
SUN YAT SEN UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, until now, researchers have not fully understood the mechanism of the occurrence and development of type 2 diabetic cardiomyopathy, and there is also a lack of effective prevention and treatment strategies and treatment measures for type 2 diabetic cardiomyopathy.
[0003] The use of disease animal models to simulate human diseases and search for potential molecular mechanisms and therapeutic targets provides great convenience for the research of human diseases. Problems such as high mortality rate, low molding rate, and large individual differences in the degree of pathological changes
For example, in the existing type 2 diabetes mouse models established by genetic modification methods, ob / ob mice with leptin knockout, db / db mice with leptin receptor knockout or KK mice with yellow obesity gene introduced are selected. -Ay mice, etc., all have the disadvantages of high cost and unavoidable restriction of related genes in application; another example is Li Xinghui et al. Distinct cardiac energy metabolism and oxidative stress adaptations between obese and non-obese type 2diabetes mellitus.[J ]. Theranostics, 2020, 10(6): 2675-2695, discloses a high-fat diet combined with streptozotocin (STZ)-induced type 2 diabetic mice, although the pathogenesis of the model is different from that of human II The pathogenesis of type 2 diabetes is similar to that of type 2 diabetes (i.e. high-fat diet and slight damage to pancreatic β cells, leading to insulin resistance and hyperglycemia), and the modeling cost is low, making it a good animal model for studying human type 2 diabetes. The animal model of type 2 diabetic cardiomyopathy has defects such as unstable blood sugar and myocardial dysfunction after 36 weeks of modeling
These problems have greatly increased the difficulty and cost of promoting research on type 2 diabetic cardiomyopathy, and have also limited the progress of research on type 2 diabetic cardiomyopathy.

Method used

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  • Construction method of rapid heart failure model of type 2 diabetes mellitus mouse
  • Construction method of rapid heart failure model of type 2 diabetes mellitus mouse
  • Construction method of rapid heart failure model of type 2 diabetes mellitus mouse

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] Embodiment 1 A kind of construction method of type 2 diabetes mouse model of rapid heart failure

[0033] 1. Experimental materials

[0034] 1.4-week-old male C57BL / 6 mice: commercially available;

[0035] 2. High-fat feed: code-named D12492, super high-fat feed containing 60% calories, the ratio of nutrients and energy of this feed is: 20% protein, 20% carbohydrate, 60% fat;

[0036] 3. Streptozotocin: Streptozotocin with a purity of HPLC ≥ 98%, dissolved in 0.1M citric acid buffer before use, adjusted to pH 4.0-4.5, and ready-to-use;

[0037] 4. AGN 193109: AGN 193109 with a purity of HPLC ≥ 98%, after a small amount of DMSO solubilization, and then diluted with corn oil to 575nMol / L.

[0038] 2. Experimental group

[0039] Seventy-five 4-week-old male C57BL / 6 mice were randomly divided into three groups, wild group, STZ group and STZ+AGN group.

[0040] Rats in the wild group were fed with common mouse chow and had free access to water and food.

[0041] Mice in S...

Embodiment 2

[0044] The detection of embodiment 2 body weight, fasting blood glucose and insulin tolerance

[0045] 1. Detection method

[0046] 5 mice were randomly selected from each group to test body weight, fasting blood glucose and insulin tolerance, and fasted for 12 hours before testing. First weigh the mice ( figure 1 A), and then use the Johnson & Johnson Wenhao blood glucose meter to measure the blood glucose value ( figure 1 B), the last intraperitoneal injection of 1IU / kg 体重 Dosage of insulin, detect and record the blood glucose values ​​at the 15th, 30th, 60th, 90th and 120th minute after the mice were injected with insulin ( figure 2 A and figure 2 B).

[0047] 2. Results analysis

[0048] Depend on figure 1 A. It can be seen that there is no difference in the weight change of the mice in the STZ group and the STZ+AGN group, and the whole process is consistent with that of the wild group mice;

[0049] Depend on figure 1 B, compared with the wild group mice, the b...

Embodiment 3

[0051] The detection of embodiment 3 heart function

[0052] Cardiac dysfunction is the main feature of type 2 diabetic cardiomyopathy. In the early stage of type 2 diabetic cardiomyopathy, diastolic dysfunction is the main feature, and in the later stage, systolic dysfunction is the main feature. Impaired left ventricular systolic function, characterized by decreased ejection fraction, is the standard for judging the development of type 2 diabetic cardiomyopathy in mice.

[0053] 1. Detection method

[0054] Five mice were randomly selected in each group to detect cardiac function, and the equipment used was Vevo 3100 small animal ultrasonic instrument. Mice were anesthetized by isoflurane inhalation. Under anesthesia, hair removal cream was used to depilate the chest of mice. The mice were placed on a constant temperature heating plate in a supine position, and isoflurane was continuously inhaled. The limbs of the mouse were connected to the electrocardiogram electrodes fo...

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Abstract

The invention provides a construction method of a rapid heart failure model of a type 2 diabetes mellitus mouse, and relates to application of AGN193109 in the aspect of construction of the rapid heart failure model of the type 2 diabetes mellitus mouse, in particular to a method for obtaining the type 2 diabetes mellitus mouse model through high fat diet and streptozotocin combined induction and then performing administration of a small molecule compound AGN193109. According to the invention, the heart failure time of the mouse is shortened by half under the condition of not adding drugs which can generate toxic and side effects on the myocardial of the mouse with type 2 diabetes mellitus, so that the purposes that the myocardial structure function is damaged in 15 weeks while the blood glucose of the mouse is stably and rapidly increased and more serious hyperglycemia, hyperlipidemia and insulin resistance are generated are achieved. The model construction method has the advantages of being fast in model forming, high in model forming rate, high in pathological change consistency degree and the like, and the constructed model can be well used as a tool for replication and research of the human type 2 diabetic myocardiopathy and has considerable necessity for related research of the type 2 diabetic myocardiopathy.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to a method for constructing a type 2 diabetic mouse model of rapid heart failure. Background technique [0002] Cardiovascular disease has seriously endangered human life and health, resulting in a heavy social and economic burden, and has become a major global public health problem. Diabetes, as one of the main risk factors for cardiovascular diseases, has attracted special attention because of its large number of patients and high mortality. According to the statistics of the International Diabetes Federation (IDF), the number of diabetic patients in the world has reached 463 million , while China is the country with the highest incidence of diabetes in the world. With the clinical application of insulin and the emergence of new treatment methods, the life span of patients with type 2 diabetes has been extended, but the myocardial injury of type 2 diabetes, which wa...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A01K67/02
CPCA01K67/02
Inventor 蔡卫斌吴燕笛黄统生李兴会
Owner SUN YAT SEN UNIV
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