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Construction process of Alzhemer's disease rat animal model

A technology of Alzheimer's disease and animal models, applied in the direction of pharmaceutical formulations, preparations for in vivo tests, etc.

Inactive Publication Date: 2005-07-13
华中科技大学同济医学院
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, there is no animal model of protein tau hyperphosphorylation induced by injection of protein kinase agonists or inhibitors into the lateral ventricle or hippocampus of rats at home and abroad, especially in combination.

Method used

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  • Construction process of Alzhemer's disease rat animal model
  • Construction process of Alzhemer's disease rat animal model
  • Construction process of Alzhemer's disease rat animal model

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0060] Example 1 intracerebroventricular injection of wortmannin (phosphatidylinositol 3-kinase inhibitor) and GF-109203X (protein kinase C inhibitor) to construct AD-like rat animal model

[0061] (1) Experimental animals and groups

[0062]Male Wistar rats (provided by the Experimental Animal Center of Tongji Medical College, Huazhong University of Science and Technology), SPF grade, weighing 250-320 grams, 150 rats, were reared in a conventional environment. Divided into ten groups, 15 rats in each group: ① normal group; ② sham operation group; ③ wortmannin group 1 (10 μM); ④ wortmannin group 2 (100 μM); ⑤ GF-109203X group 1 (10 μM); ⑥ GF-109203X group 2 (100 μM); ⑦wortmannin(10μM)+GF-109203X(10μM) group 1; ⑧wortmannin(10μM)+GF-109203X(100μM) group 2; ⑨wortmannin(100μM)+GF-109203X(10μM) group 3; (100 μM) Group 4.

[0063] (2) Main reagents

[0064] Acrylamide (Arc), N,N-Methylenebisacryloyl (bis), Tetramethylethylenediamine (TEMED), Sodium Dodecyl Sulfate (SDS), Glycine ...

example 2

[0092] Example 2 Establishing an AD-like rat animal model by injecting wortmannin and GF-109203X into the hippocampus

[0093] (1) Experimental animals and groups

[0094] Male Wistar rats (provided by the Experimental Animal Center of Tongji Medical College, Huazhong University of Science and Technology), SPF grade, weighing 250-320 grams, 150 rats, were reared in a conventional environment. Divided into ten groups, 15 rats in each group: ① normal group; ② sham operation group; ③ wortmannin group 1 (1 μM); ④ wortmannin group 2 (10 μM); ⑤ GF-109203X group 1 (1 μM); ⑥ GF-109203X group 2 (10 μM); ⑦wortmannin(1μM)+GF-109203X(1μM) group 1; ⑧wortmannin(1μM)+GF-109203X(10μM) group 2; ⑨wortmannin(10μM)+GF-109203X(1μM) group 3; ⑩wortmannin(10μM)+GF-109203X (10 μM) Group 4.

[0095] (2) main reagent and instrument are the same as example 1

[0096] (3) Administration by hippocampal injection Follow the steps below:

[0097] ①Wistar rats were anesthetized by intraperitoneal injectio...

example 3

[0106]Example 3 Injection of trans-isoproterenol ((-) Isoproterenol, IP) into the lateral ventricle, and intraperitoneal injection of nimodipine 1 h before and 6 h after the injection of trans-isoproterenol to establish an AD-like rat animal model

[0107] (1) Experimental animals and groups

[0108] Male Wistar rats (provided by the Experimental Animal Center of Tongji Medical College, Huazhong University of Science and Technology), weighing 250 to 320 grams, were reared in a conventional environment. Experimental rats were randomly divided into seven groups, 15 in each group: normal group; NS injection 24h group (sham operation control group, C-24h), IP injection+NIM intraperitoneal injection 24h group (IP+NIM 24h), NIM intraperitoneal injection 24h group (NIM 24h); NS injection 48h group (C-48h), IP injection+NIM intraperitoneal injection 48h group (IP+NIM 48h), NIM intraperitoneal injection 48h group (NIM 48h). The intraperitoneal injection of nimodipine was carried out 1...

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Abstract

The present invention provides method of constructing Alzhemer's disease (AD) rat animal model through injecting wortmanin as phosphatidylinositol 3 kinase inhibitor and GF-109203X as protein kinase C inhibitor into rat lateral ventricle simultaneously. The method can induce AD-like abnormal excessive phosphorylation of hippocampal skelemin and neurofibrillary tangle-like pathologic changes and constitute rat animal model with co-existed learning and memory disorder. The model may be used in screening medicine for treating Alzhemer's disease and in the research of the internal relation between protein kinase and AD pathogenesis.

Description

technical field [0001] The invention belongs to the technical field of medical evaluation and detection, and specifically relates to a kind of progeria for screening abnormal hyperphosphorylation of skeleton protein Tau AD, neurofibrillary tangle-like pathological changes, and learning and memory disorders caused by excessive activation of protein kinases. The establishment of animal models of dementia for the screening of therapeutic drugs, and the study of the intrinsic link between protein kinases and the pathogenesis of AD. technical background [0002] Alzheimer's disease (AD) is a common neurodegenerative disease, the main symptoms of which are memory loss, low cognitive ability and slow thinking, and progressive aggravation, and finally unable to take care of themselves and die, the course of the disease is generally 5 ~20 years. With the acceleration of the aging process of society, the incidence and number of AD have risen sharply, and it has become a serious disea...

Claims

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Application Information

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IPC IPC(8): A61K49/00
Inventor 王建枝
Owner 华中科技大学同济医学院
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