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A kind of construction method of hyperuricemia model

A technology of hyperuricemia and construction method, applied in the field of experimental model construction, can solve the problems of skin and mucous membrane liver damage, hyperuric acid instability, long-term maintenance of hyperuricemia model, avoiding animal damage, and the method is safe and reliable. , the effect of good application prospects

Active Publication Date: 2019-12-03
QINGDAO UNIV
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AI Technical Summary

Problems solved by technology

Hyperuricemia is usually used as a sign of gout clinically. Among the patients with hyperuricemia, 5% to 12% of them will eventually develop gout. Benzbromarone, etc., but these drugs all have certain toxic and side effects, such as causing lipid peroxidation damage in the body, and causing greater damage to the skin and mucous membranes, hematopoietic system, kidneys and liver; therefore, new drugs for the treatment of gout Research has received high attention, and establishing a stable and continuous hyperuricemia model is an important prerequisite for research on hyperuricemia and gout
[0003] At present, the mechanism of the commonly used hyperuricemia model construction method generally involves supplementing exogenous uric acid, supplementing uric acid precursors, inhibiting uricase activity, and inhibiting renal uric acid excretion, etc., such as using yeast and purines such as adenine and hypoxanthine Substances, or direct administration of exogenous uric acid to build models; however, because rats, mice and other mammals that are often used as experimental subjects have uricase that humans lack, in medium and long-term experiments, the activity of uricase is activated, making the blood The uric acid level cannot be maintained at a high level; in recent years, the most commonly used hyperuricemia model drug at home and abroad, oxonate potassium, can competitively combine with uricase, inhibit the activity of uricase, and reduce the blood uric acid level in the body. It increases in a short period of time and can be maintained for a long time; however, due to its competitive inhibition mechanism, long-term administration is required, which can cause strong inflammatory reactions and other adverse effects on the kidneys of experimental animals; currently the most commonly used drugs to inhibit uric acid excretion are mainly For the anti-tuberculosis drugs ethambutol and niacin, the disadvantage of this model construction method is that substances such as ethambutol and niacin can cause liver damage
[0004] Epidemiological surveys have shown that the intake of fructose is increasing year by year, and there is a certain correlation between the increase in fructose consumption and the increase in the average level of blood uric acid in the population. In addition, high fructose diets are associated with hypertension, diabetes, atherosclerosis There is a certain relationship between the occurrence of metabolic diseases such as cirrhosis and abdominal obesity; some studies have shown that 10% fructose water can increase the blood uric acid level of rats, but the high uric acid level formed is extremely unstable, so it is difficult to serve as an ideal Animal models of hyperuricemia are widely used; and the method of using a single drug to build a model often cannot achieve good results due to its single mechanism of action. The hyperuricemia model lasts longer, the blood uric acid rises more obviously, and it is closer to the mechanism and actual situation of human hyperuricemia; therefore, the method of high purine-containing yeast combined with a high fructose diet is used to induce hyperuricemia Blood disease, forming a stable animal model, can provide good technical support for the research on uric acid metabolism, intervention effect and its mechanism, and it is also the subject task of current academic circles

Method used

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  • A kind of construction method of hyperuricemia model
  • A kind of construction method of hyperuricemia model
  • A kind of construction method of hyperuricemia model

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0016] Example 1: The specific steps for constructing a hyperuricemia model in this example are

[0017] (1) Animal sample selection and model construction: 8-week-old male clean-grade Wistar rats, weighing (200±20) g, purchased from Shandong Lukang Pharmaceutical Co., Ltd., and fed with SPF animals at Qingdao University School of Medicine In the breeding room, the normal rat pellets were used for adaptive feeding for 1 week before the start of the experiment. During the experiment, the body surface characteristics of the rats and whether there were any abnormal changes in behavioral activities were observed. Abnormal rats were isolated, and finally the body after adaptive feeding was selected. 40 Wistar rats with no abnormalities in appearance characteristics and behavioral activities; the adaptive feeding environment is: temperature: 20~24℃, relative humidity: 50%~70%, light rhythm: 12D: 12L, working illumination: 150~ 300lx, airflow, wind speed 0.1~0.2m / s, noise ≤60dB; the ada...

Embodiment 2

[0021] In this example, 40 male Wistar rats were grouped according to their body weight by random number table method. They were 4 groups of blank control, yeast control, yeast oxazinate potassium, and yeast fructose, each with 10 rats. The blank control group was given normal rats. Rats were fed pellets, and the other three groups were fed with yeast feed with a mass fraction of 0.2; rats in the yeast fructose group were given 10% fructose drinking water by mass, and the other three groups were given tap water drinking; the high yeast oxazinate potassium group was given 0.5g / ( kg·d) potassium oxoxamate was given by gavage, the other three groups were given distilled water by gavage, the gavage volume was 10ml / (kg·d); all rats were free to drink and eat; after feeding 2, 4, 6 At 8 o'clock in the morning of 8W, the rats were fasted for 12 hours and then cut their tails to collect 1.0~1.5ml of blood. They were allowed to stand for coagulation at room temperature, centrifuged at 30...

Embodiment 3

[0036] In this example, the animal intervention of Example 1 was used for the experiment: at the end of the 8th week of the animal experiment, after the rats were fasted for 12 hours, the rats were sacrificed, and the right kidneys of each group of rats were removed, fixed with 4% paraformaldehyde, and conventional paraffin wax. After embedding, make 3μl thick sections, stain with HE and observe under light microscope (×400); the results are as attached figure 2 As shown, in the blank control group and the yeast control group, the kidney structure of the rats is normal, the glomeruli in the renal cortex are evenly distributed, the size is normal, and the renal tubules are not swollen or degenerated; the kidney of the yeast oxazinate potassium group has occasional interstitial foci. Mononuclear lymphocyte infiltration, no obvious fibrosis; occasional crystal deposits in the renal tubular interstitium of rats in the yeast fructose group, no obvious fibrosis; comprehensive conclusi...

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Abstract

The invention belongs to the technical field of experimental model construction, and relates to a construction method capable of being used for quickly constructing a long-term and stable hyperuricemia model. A technological process of the method comprises the four steps of selecting samples, adaptively feeding, constructing the model, and applying the model, and concretely comprises the steps of adaptively feeding selected rats in an SPF animal feeding room for 3 to 7 days, observing body surface characteristics and behavioral activities of the rats, and reserving qualified sample rats; feeding the qualified sample rats with a yeast feed with the mass percentage being 20 percent and fructose water with the mass percentage being 10 percent or correspondingly proportional fresh fruit juice, and enabling the rats to take food and drink freely, thus obtaining the sample rat hyperuricemia model; applying the constructed rat hyperuricemia model, thus obtaining a model with representative illness representations. By adopting the method combining feed and drinking water for modelling, the operation is simple and easy to grasp, animal injuries caused by long-time gavage or injection are avoided, and the method is safe and reliable, and has a favorable application prospect.

Description

Technical field: [0001] The invention belongs to the technical field of experimental model construction, and relates to a method for quickly constructing a long-term stable hyperuricemia model, in particular to a method for constructing a hyperuricemia model using rats as a sample. Background technique: [0002] In recent years, with the improvement of people’s living standards and changes in dietary patterns, the incidence of hyperuricemia has increased year by year; multiple epidemiological survey results have shown that hyperuricemia is a cardiovascular disease, kidney disease, diabetes, etc. The independent risk factors of metabolic syndrome have become a health problem threatening the quality of human life worldwide. Hyperuricemia is usually used as a clinical sign of gout. Among the patients with hyperuricemia, 5% to 12% will eventually develop gout; for the current treatment of gout, common clinical drugs include allopurinol and Benzbromarone, etc., but these drugs all ha...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A01K67/02
CPCA01K67/02
Inventor 马爱国别凤仪孙永叶张华琦
Owner QINGDAO UNIV