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Application of bone morphogenetic protein-9 in preparing pharmaceutical composition for treating and/or preventing cholinergic system degeneration related diseases

A cholinergic and composition technology, applied in the field of bone morphogenetic protein-9, can solve problems such as the application of bone morphogenetic protein-9 that has not yet been reported, and achieve the effects of avoiding first-pass effect, improving memory and cognitive ability, and being easy to popularize

Inactive Publication Date: 2017-03-08
ZHONGSHAN HOSPITAL FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] However, the application of bone morphogenetic protein-9 in the treatment of diseases related to cholinergic system degeneration has not been reported so far.

Method used

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  • Application of bone morphogenetic protein-9 in preparing pharmaceutical composition for treating and/or preventing cholinergic system degeneration related diseases
  • Application of bone morphogenetic protein-9 in preparing pharmaceutical composition for treating and/or preventing cholinergic system degeneration related diseases
  • Application of bone morphogenetic protein-9 in preparing pharmaceutical composition for treating and/or preventing cholinergic system degeneration related diseases

Examples

Experimental program
Comparison scheme
Effect test

experiment example 1

[0031] Experimental example 1 Establishment of a mouse model of cholinergic neuron (BFCS) degeneration

[0032] Select 40 12-week-old male C57 mice (inbred mice) and randomly divide them into control group (Con), thiamine-deficient group (PTD), BMP-9 group, thiamine-deficient + BMP-9 group (PTD+BMP-9), 10 mice in each group, all animals were kept in SPF (Specific Pathogen Free) grade room at room temperature 25°C between light and dark for 12h, free to eat and drink.

[0033] The control group was given normal diet + intraperitoneal injection of normal saline 5 μL / (g.d); the thiamine-deficient group was given thiamine-deficient feed + intraperitoneal injection of pyrithiamine 0.5 μg / (g.d); the BMP group was given normal diet + intraperitoneal injection of normal saline 5 μL / (g.d) + nasal drop of 1ng / (g.d) BMP-9; thiamine-deficient + BMP-9 group was given thiamine-deficient feed + intraperitoneal injection of pyrithiamine 0.5 μg / (g.d) + nasal drop Add 1ng / (g.d) of recombinant ...

experiment example 2

[0036] Experimental example 2 Morris water maze detection

[0037] On the 5th day after nasal administration, the Morris water maze test was started. The specific inspection methods are as follows:

[0038](1) Training stage: Put the mouse head into the water with its head facing the pool wall, and record the time when the mouse reached the underwater platform, the distance traveled to the platform and the average swimming speed. If the mouse did not find the platform within 60 s, Guide the mouse to the platform, and take it away after it stays on the platform for 20 s. If the mouse reaches the platform within 60 s, let it stay on the platform for 15 s, and then take it out. Training 8 times, each training time interval is 30 minutes, training a total of 5 days.

[0039] (2) Platform withdrawal experiment: the platform was evacuated, the space exploration training was started for 60 s, and the time for the mice to find the platform hidden under the water surface (escape laten...

experiment example 3

[0050] Experimental example 3 Immunofluorescence staining

[0051] After the mice were anesthetized, the thoracotomy was intubated to the ascending aorta, and then perfused with 60 mL of normal saline, and then fixed with 100 mL of 4% paraformaldehyde. Place in 20% and 30% sucrose solution in turn until the tissue sinks to the bottom, and after embedding in OCT (Optimal Cutting Temperature Compound, a water-soluble mixture of polyethylene glycol and polyvinyl alcohol), perform coronal sectioning on a frozen microtome, take drift Immunofluorescence staining was performed on the slices. The brain slices were rinsed with 0.01M PBS (phosphate buffered saline) and permeabilized with 0.3% Triton-X100 (polyethylene glycol octylphenyl ether) for 30 minutes, and blocked with 5% normal donkey serum for 1 hour. Add goat anti-ChAT (acetylcholine transferase) (1:200, Millipore ® ), incubated overnight at 4°C, rinsed with 0.01M PBS and added TRITC (tetramethylrhodamine isothiocyanate)-labe...

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Abstract

The invention discloses an application of bone morphogenetic protein-9 in preparing a pharmaceutical composition for treating and / or preventing cholinergic system degeneration related diseases. The cholinergic system is a central cholinergic neuronal system; and the cholinergic system degeneration related diseases include Alzheimer's disease. The bone morphogenetic protein-9 is subjected to nasal administration. According to the application of the bone morphogenetic protein-9 in preparing the pharmaceutical composition for treating and / or preventing the cholinergic system degeneration related diseases disclosed by the invention, the bone morphogenetic protein-9 is capable of significantly increasing the number of medial septum cholinergic neurons, the expression content of choline acetyl transferase in a brain, the activity of the choline acetyl transferase and the release amount of acetyl choline, and in addition, the bone morphogenetic protein-9 is capable of obviously improving cognitive and memory capacities of a mouse with cholinergic system degeneration.

Description

technical field [0001] The invention relates to bone morphogenic protein-9, in particular to the use of bone morphogenic protein-9 as a pharmaceutical composition for treating and / or preventing diseases related to cholinergic system degeneration. Background technique [0002] Alzheimer's disease (AD) is the most common neurodegenerative disease in the world today. Its main clinical manifestation is progressive cognitive decline, causing serious harm to individuals, families and society. So far, the pathogenesis of AD is still not completely clear, and a variety of hypotheses have been formed, such as Aβ hypothesis, tau protein hypothesis, cholinergic hypothesis and so on. However, all current clinical trials based on the Aβ hypothesis and the tau protein hypothesis have ended in failure. The widely used clinical cholinesterase inhibitors cannot prevent the progression of AD, so the pathogenesis of AD must be rethought. [0003] More and more studies have confirmed that the ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/18A61P25/28
CPCA61K9/0043A61K38/1875
Inventor 钟春玖王子高
Owner ZHONGSHAN HOSPITAL FUDAN UNIV
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