Application of sodium butyrate in preparation of product for treating DYT25 dysmnesia

Abstract

The invention belongs to the technical field of medicines, and particularly provides a novel application of sodium butyrate in preparation of a product for treating DYT25 dysmnesia. DYT25 muscular dystonia mouse (Gal + / -) experiment evaluation proves that the sodium butyrate can obviously increase the falling time, the learning rate and the initial coordination in an accelerated bar rotating experiment; the descending time and the turning time in a vertical rod experiment are remarkably shortened, and the passing time and the sliding frequency in a horizontal rod experiment are shortened; and the movement distance and the average speed in an open field experiment are increased. Therefore, the sodium butyrate provided by the invention can be applied to preparation of products for treating DYT25 dysmnesia.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of medicine, and specifically discloses a use of sodium butyrate in preparation of a product for treating DYT25 dystonia. BACKGROUND

[0002] Dystonia is the third most common movement disorder after primary tremor and Parkinson's disease. Among them, DYT25 dystonia is an autosomal dominant subtype caused by GNAL gene mutation. Guanosine-binding protein G (olf) subunit alpha (Gα olf ) encoded by the GNAL gene plays a key role in striatal signaling, and the striatum is an important organization for controlling motor ability. However, there are currently limited treatment options for dystonia, and it is an urgent technical problem to develop a drug or functional food that can be used to prevent and treat DYT25 dystonia.

[0003] Butyric acid is a short-chain fatty acid, which is mainly produced by intestinal microorganisms fermenting dietary fiber in the body, and also exists in large quantities in dairy products such as whole milk, butter and cheese. In the human body, more than 90% of butyrate is absorbed by colon cells through monocarboxylate transporters (MCTs) or sodium-coupled monocarboxylate transporters (SMCTs) and used as an energy source for these cells. In recent years, butyric acid has been found to have a variety of biological activities, including metabolic regulation, anti-inflammatory and antioxidant, immune regulation function, and anticancer effects. Because butyric acid is unstable in nature, butyrate is often used as a butyric acid supplement in practical applications, and sodium butyrate is one of the most widely used butyrate salts. Existing studies have shown that butyrate can activate GPCR on intestinal endocrine cells to enhance the secretion of GLP-1 and PYY in the intestine, and play an anti-obesity role. In addition, in clinical and animal experiments, butyrate can inhibit pro-inflammatory cytokines IFN-γ, TNF-α, IL-1β, IL-6 and IL-8, and play an anti-inflammatory role. However, the prevention and treatment effects of sodium butyrate on dystonia have not been reported. SUMMARY

[0004] The purpose of the present application is to provide a new use of sodium butyrate, specifically, the use of sodium butyrate in the preparation of a product for treating DYT25 dystonia.

[0005] In order to achieve the above-mentioned purpose, the technical scheme adopted by the present application is:

[0006] The use of sodium butyrate in the preparation of a product for treating DYT25 dystonia.

[0007] Preferably, the sodium butyrate can increase the falling time, learning rate and initial coordination in the accelerating rotarod test; significantly reduce the falling time and turning time in the vertical pole test, reduce the passing time and the number of slips in the horizontal pole test, and improve the motor coordination.

[0008] Preferably, the sodium butyrate can increase the movement distance and average speed of mice in the open field test, and improve the spontaneous motor ability.

[0009] The present application also provides a health food composition for improving DYT25 dystonia, which comprises the sodium butyrate according to any one of the above, and a food acceptable excipient.

[0010] Preferably, the health food composition can increase the falling time, learning rate and initial coordination in the accelerating rotarod test; significantly reduce the falling time and turning time in the vertical pole test, reduce the passing time and the number of slips in the horizontal pole test; and increase the movement distance and average speed in the open field test.

[0011] The present application also provides a pharmaceutical composition for treating DYT25 dystonia, which comprises the sodium butyrate according to any one of the above, and a pharmaceutically acceptable excipient or carrier.

[0012] Preferably, the medicine can be an oral liquid, a powder, a tablet, a capsule or an injection.

[0013] Compared with the prior art, the present application has the following beneficial effects:

[0014] The present application finds a new use of sodium butyrate. Animal experiment results show that supplementing sodium butyrate at an addition amount of 1000 mg / kg for 12 weeks can significantly increase the falling time, learning rate and initial coordination in the accelerating rotarod test; significantly reduce the falling time and turning time in the vertical pole test, reduce the passing time and the number of slips in the horizontal pole test; and increase the movement distance and average speed in the open field test, indicating that sodium butyrate can treat DTY25 dystonia. The present application provides a new use of sodium butyrate in preparing related health food and medicines with the effect of treating DTY25 dystonia. BRIEF DESCRIPTION OF DRAWINGS

[0015] Figure 1 Effects of sodium butyrate on the body weight of DYT25 dystonia mice.

[0016] Figure 2 Results of the accelerating rotarod test of the three groups of mice; wherein A is the accelerating rotarod falling time, B is the learning speed, and C is the initial coordination. * p < 0.05, ** p < 0.01, *** p < 0.001,**** p < 0.0001.

[0017] Figure 3 The vertical rod experiment results of three groups of mice; wherein, A is the falling time, and B is the turning time. ** p < 0.01, *** p < 0.001.

[0018] Figure 4 The horizontal rod experiment results of three groups of mice; wherein, A is the passing time, and B is the sliding frequency. * p < 0.05, ** p < 0.01, *** p < 0.001.

[0019] Figure 5 The open field experiment results of three groups of mice; wherein, A is the total distance of movement, and B is the average speed. ** p < 0.01, *** p < 0.001.

[0020] Note: the present application Figures 1-5 in which:

[0021] WT represents the control group, and physiological saline is intragastrically administered;

[0022] HE represents the model group, and physiological saline is intragastrically administered;

[0023] NaB represents the sodium butyrate intervention group, and 1000 mg / kg of sodium butyrate is intragastrically administered, and the solvent is physiological saline. DETAILED DESCRIPTION

[0024] The present application will be further described below in conjunction with the embodiments of the present application and the accompanying drawings. However, the protection scope of the present application is not limited to this.

[0025] Example 1

[0026] Effect of sodium butyrate on the body weight of mice

[0027] 9 wild type mice (WT) and 18 Gnal heterozygote mice (HE) were raised under specific pathogen-free (SPF) conditions (environmental temperature 22±2℃, relative humidity 40-70%, 12 h-12 h light-dark cycle). The Gnal heterozygote mice (HE) were divided into a model group and a sodium butyrate intervention group, each group having 9 mice. The sodium butyrate intervention group was intragastrically administered with 1000 mg / kg of sodium butyrate, and the control group and the model group were both intragastrically administered with an equal amount of physiological saline. The intragastric administration was performed once a day, and the experimental period was 12 weeks. During the experimental period, all mice had free access to food and water, and the final body weight of the mice was recorded.

[0028] According to Figure 1As shown, compared with the model group, sodium butyrate supplementation had no significant effect on the body weight of dystonia mice.

[0029] Example 2

[0030] Effect of butyric acid on motor coordination of dystonia mice

[0031] After 12 weeks of gavage in Example 1, mice were subjected to accelerated rotarod, vertical pole and horizontal pole experiments.

[0032] (1) The specific steps of the accelerated rotarod experiment are as follows: the mouse is gently placed on the stationary rotarod, and after confirming that the mouse is standing, the accelerated rotarod program is started: the rotarod is accelerated from 4 rpm to 40 rpm within 5 minutes, and the falling time of the mouse from the rotarod is recorded. Each mouse is subjected to three rounds of experiments (with an interval of 30 min), and the experiment is performed continuously for four days, and before the next experiment, the rotarod rod is wiped with a 75% ethanol solution and dried. After all the data are measured, statistical analysis is performed, and the learning rate and initial coordination are calculated by regression analysis.

[0033] (2) The specific steps of the vertical pole experiment are as follows: the mouse is placed head-up on the top of the vertical pole, and the bottom of the pole is fixed in a mouse cage with bedding. When the mouse grips the vertical pole with all four paws, it is released, and the mouse will climb down the pole to return to the cage. The time from "head up" to completely turning the body upside down to "head down" (turning time) and climbing back to the cage (descending time) is recorded. During the experiment, each mouse is subjected to three rounds of experiments (with an interval of 30 min), and after all the data are measured, statistical analysis is performed.

[0034] (3) The specific steps of the horizontal pole experiment are as follows: the mouse is placed on a 1.5 cm diameter circular horizontal pole for testing. The horizontal pole is 40 cm high from the ground, and the end of the horizontal pole is a black box with an opening (20 cm 3 ). The mouse will start from the starting point of the horizontal pole, cross the horizontal pole to reach the end point (passing time), and the number of slips during the process is recorded. During the experiment, each mouse is subjected to three rounds of experiments (with an interval of 30 min), and after all the data are measured, statistical analysis is performed.

[0035] According to Figure 2 As shown, in the accelerated rotarod, compared with the control group mice, the falling time of the model group mice in the 5th-12th experiment was significantly reduced, and at the same time, butyric acid supplementation could significantly increase the falling time of the mice. Linear regression analysis was performed on the data of each mouse, and the intercept (initial coordination) and slope (learning rate) were calculated, and the results showed that compared with the control group mice, the initial coordination and learning rate of the model group mice were significantly decreased, and at the same time, butyric acid supplementation could significantly improve the initial coordination and learning rate of the mice Figure 2 B-C). According to Figures 3-4As shown, compared with the control group mice, the falling time, turning time, passing time and the number of slipping of the model group mice were significantly increased, while the butyric acid supplement could significantly increase the above indexes. The results showed that compared with the control group mice, the motor coordination ability of the model group mice decreased, and the butyric acid supplement could significantly improve the motor coordination of the mice.

[0036] Example 3

[0037] Effect of butyric acid on spontaneous motor activity of mice with dystonia

[0038] The mice in Example 1 were subjected to open field test after intragastric administration for 12 weeks. The specific steps of the open field test are as follows: the mice were placed in a 40x40 cm open field, and each mouse was adapted to the environment for 5 min before the experiment. After the adaptation, the activity of the mice in the open field was monitored and recorded for 30 min using a camera system, and the trajectory tracking and data acquisition were performed to analyze the total movement distance and average movement speed of the mice. After the end, the mice were taken out, the open field area was wiped with 75% ethanol solution and dried before the next experiment, and statistical analysis was performed after all the data were measured.

[0039] According to Figure 5 As shown, compared with the control group, the total movement distance and average speed of the model group mice were significantly decreased, indicating that the mice with dystonia had reduced spontaneous motor activity; the butyric acid supplement could increase the total movement distance and average speed of the mice, indicating that the butyric acid had the effect of improving the spontaneous motor behavior of the mice.

[0040] Example 4

[0041] The present application is not limited to the above-mentioned embodiments, and any modification, improvement or replacement that can be conceived by those skilled in the art without departing from the essential content of the present application falls within the scope of the present application.

Claims

1. Use of sodium butyrate in the preparation of products for treating DYT25 dystonia.

2. The use according to claim 1, characterized in that, The sodium butyrate can treat the DYT25 dystonia mouse model (Gnal + / - (behavioral characteristics) 3. The use according to claim 2, characterized in that, The sodium butyrate can improve motor coordination defects in DYT25 dystonia mice.

4. The use according to claim 2, characterized in that, The sodium butyrate can improve the spontaneous movement ability of DYT25 dystonia mice.

5. The use according to claim 1, characterized in that, The product is a health food composition or a pharmaceutical composition.

6. A health food composition for preventing DYT25 dystonia, characterized in that, It includes sodium butyrate as described in any one of claims 1-5, and food-acceptable excipients.

7. The health food composition according to claim 6, characterized in that, The health food composition can increase the fall time, learning rate, and initial coordination in the accelerated rotundus test; and significantly reduce the descent time and turning time in the vertical bar test, and reduce the passage time and number of falls in the horizontal bar test. In addition, it increases the distance traveled and the average speed in open field experiments.

8. A pharmaceutical composition for preventing DYT25 dystonia, characterized in that, It includes sodium butyrate as described in any one of claims 1-5, and pharmaceutically acceptable excipients or carriers.

9. The medicament for preventing DYT25 dystonia according to claim 8, characterized in that, The drug may be an oral liquid, powder, tablet, capsule, or injection.

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