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Method for constructing acute kidney injury (AKI) model of miniature pigs

A technology for acute kidney injury and its construction method, applied in animal husbandry and other directions, can solve the problems of not being able to simulate human kidney disease well, not being able to reflect the effectiveness well, and not be able to simulate the pathogenesis well, and to achieve model establishment. The effect of short time, small damage to model animals and simple operation

Inactive Publication Date: 2020-07-28
GENERAL HOSPITAL OF PLA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0003] At present, cisplatin-AKI models are mostly constructed by rodents (rats, mice). The constructed kidney disease model cannot simulate human kidney disease well. Therefore, in the process of seeking treatment and protection measures for corresponding human kidney disease, this rodent model cannot well reflect its role in the human body. effectiveness
[0004] In addition, the cisplatin-AKI model in rodents is usually established by intraperitoneal injection, which is significantly different from the way of clinical cisplatin administration for human treatment, and the cisplatin in rodents -The AKI model cannot observe other organs other than the kidney and the systemic response, so it cannot well simulate the pathogenesis of AKI caused by cisplatin

Method used

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  • Method for constructing acute kidney injury (AKI) model of miniature pigs
  • Method for constructing acute kidney injury (AKI) model of miniature pigs
  • Method for constructing acute kidney injury (AKI) model of miniature pigs

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Embodiment 1

[0034] Since there is no authoritative research on the minipig acute kidney injury (AKI) model and related model construction methods in the prior art, in order to obtain the present invention, the inventor firstly uses the prior art small and medium-sized animal (such as mice) model The usual way of intraperitoneal injection is used as the way of administration to explore the establishment of a miniature pig acute kidney injury (AKI) model, and at the same time to explore the dose of cisplatin.

[0035] The exploratory experiment is as follows:

[0036] (1) Configure cisplatin with physiological saline as a cisplatin solution of 1 mg / ml, place it on a shaker at a speed of 50 r / min and shake at room temperature for 30 minutes after configuration, and then filter through a 0.22 μm filter to remove impurities and bacteria for use; the cisplatin solution It should be prepared and used immediately, and it needs to be wrapped in tin foil and stored at room temperature;

[0037] (2...

Embodiment 2

[0047] Based on the previous experiments that proved that the intraperitoneal injection method cannot be used for the construction of acute kidney injury (AKI) in miniature pigs, the applicant is now creatively trying to use the intravenous administration method for the first time, especially the post-auricular intravenous administration method suitable for miniature pigs, to carry out model building.

[0048] For the exploration of cisplatin dose, the survival rate of miniature pigs in each experimental group mentioned above is as follows: Figure 4 Shown, wherein 4mg / kg and 6mg / kg experiment group all occur miniature pig death (4mg / kg experiment group dies 1 / 3, 6mg / kg experiment group dies 2 / 3), 2.5mg / kg and 3.5mg / kg experiment There was no death of miniature pigs in the group, which indicated that the lethal dose of cisplatin dose was around 4 mg / kg in miniature pigs; meanwhile, figure 2 It showed that the increase of creatinine and blood urea nitrogen detection values ​​...

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Abstract

The invention relates to a method for constructing an acute kidney injury (AKI) model of miniature pigs. Cisplatin at a dosage of 3.8-4.0 mg / kg is adopted for the first time, the male Ba-ma mini-pigsare selected as objects for constructing the model, and the acute kidney injury (AKI) model of the miniature pigs is constructed successfully in a mode of opisthotic intravenous injection. The acute kidney injury (AKI) model of the miniature pigs is constructed successfully for the first time, the problem is solved that an rodent model in the prior art has large differences from human acute kidneyinjuries in genetics, kidney anatomy morphology, physiology, administration modes, pathogenic mechanisms and other aspects, a closer and more reliable animal model for preclinical research of drugs is provided for study of the human acute kidney injuries, and a basis is provided for earlier prevention and treatment of cisplatin-AKI in clinical patients.

Description

technical field [0001] The application relates to a method for constructing a miniature pig acute kidney injury (acute kidney injury, AKI) model, which belongs to the technical field of animal models. Background technique [0002] Cisplatin is a highly effective antineoplastic drug, currently mainly used in the treatment of bladder cancer, cervical cancer, non-small cell lung cancer and other malignant tumors. However, due to serious side effects such as nephrotoxicity, neurotoxicity, ototoxicity and teratogenicity, the clinical application of cisplatin is limited. Renal toxicity is the main limiting factor, about 25%-35% of patients receiving a single dose of cisplatin have impaired renal function, manifested as a 20-40% decrease in glomerular filtration, increased serum creatinine and blood urea nitrogen concentrations, etc. Acute kidney injury (AKI) manifests, and current renal protection measures are not satisfactory in patients receiving cisplatin chemotherapy. AKI is...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A01K67/027
CPCA01K67/027A01K2207/20A01K2227/108A01K2267/03
Inventor 王思扬蔡广研陈香美
Owner GENERAL HOSPITAL OF PLA
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