CN107456572B

CN107456572B - Application of fully carboxylated osteocalcin in preparation of rapid antidepressant drug

Info

Publication number: CN107456572B
Application number: CN201710248936.XA
Authority: CN
Inventors: 谢鹏; 郑鹏; 周婵娟; 潘俊希
Original assignee: Chongqing Medical University
Current assignee: Chongqing Medical University
Priority date: 2017-04-17
Filing date: 2017-04-17
Publication date: 2020-04-21
Anticipated expiration: 2037-04-17
Also published as: WO2018192428A1; CN107456572A

Abstract

The invention discloses application of fully carboxylated osteocalcin in preparation of a rapid antidepressant. In a physiological state, the mouse is injected intraperitoneally with osteocalcin in C57BL/6 male, and compared with a control group injected with normal saline, the behavioral test shows that the forced swimming and tail suspension immobility time of the mouse is obviously reduced (p is less than 0.05) after the mouse is administered with fully carboxylated osteocalcin (80ng/g) for half an hour, which indicates that the fully carboxylated osteocalcin has a quick antidepressant effect, and provides a basis for developing a new quick-acting antidepressant.

Description

Application of fully carboxylated osteocalcin in preparation of rapid antidepressant drug

Technical Field

The invention relates to the field of medicines, in particular to a novel antidepressant with quick response.

Background

The main expression is that ① has slow clinical effect and has a delay effect, and the antidepressant can be clinically taken for 2-3 weeks generally, ② treatment response rate is low, the antidepressant is only used for 1/3 patients to treat the first antidepressant, ③ has obvious resistance phenomenon, refractory depression becomes a big problem in the treatment of the depression, ④ increases the suicide risk of the depression patients, especially the green patients, and the limitation causes the compliance of the depression patients in the treatment process to be extremely low, so that the functions and the social functions of the patients are difficult to recover, the family and the society are hard to be seriously and the economic burden is brought, the body of the people can see the urgent need to treat the depression, and the body of the people can see the great social burden of the depression.

Osteocalcin is an important component of the extracellular matrix of bone and is a non-collagenous protein that is most abundant in bone. Osteocalcin is an endocrine regulating hormone involved in regulating the physiological processes of energy metabolism, male fertility and brain development.

Disclosure of Invention

In view of this, the object of the present invention is to demonstrate a fast acting antidepressant, namely the use of fully carboxylated osteocalcin in the preparation of a fast antidepressant. Thereby providing a new theoretical basis for developing a new generation of antidepressant with quick response, good safety and good curative effect.

The invention provides a fast-acting antidepressant, which comprises fully carboxylated osteocalcin.

In the invention, after 80ng/g of fully carboxylated osteocalcin is injected into the abdominal cavity for 30 minutes, the mice have a quick antidepressant effect, and the immobility time of forced swimming and tail suspension experiments is obviously shortened compared with that of a normal control group. This provides the basis for the development of novel rapid antidepressant drugs.

Drawings

FIG. 1 is a graph showing the results of a forced swimming test;

FIG. 2 is a graph showing the results of the tail suspension experiment.

Detailed Description

The effect of fully carboxylated osteocalcin according to the invention is further illustrated by specific experiments below.

1. Experimental animals: adult male C57BL/6 mice weighing an average of 22-25g each. The first two weeks were acclimatized in a Specific Pathogen Free laboratory animal room (SPF).

3. The main reagents are as follows: 80ng/g carboxylated osteocalcin, 30mg/kg ketamine and physiological saline.

4. Design of experiments

Male C57BL/6 mice, 6 weeks old, were randomly divided into five groups, including saline (negative control, n-20), three fully carboxylated osteocalcin (n-20 per group) and ketamine (positive control, n-20). The administration concentration is as follows: the osteocalcin administration concentrations in the three fully carboxylated osteocalcin groups were 8ng/g, 20ng/g and 80ng/g, respectively, and the ketamine administration concentration was 30 mg/kg. Each group was administered with intraperitoneal injections of the drug-six times a day, and behavioral assessments (forced swimming, tail suspension experiments) were performed 30min after the sixth administration. All behavioral recordings used a video surveillance System (SMART).

Forced swimming: the test was performed for a total of 6 minutes: the first minute is the adaptation stage in water; starting from the second minute, 5 minutes were counted, and the number of times and the total duration of the two groups of mice kept in a static posture in water for 5 minutes were calculated, and the longer the total static time, i.e., the immobility time, represents the stronger the despair sense of the mice, meaning the more severe the depression symptoms of the mice.

Tail suspension experiment: before each group of mice experiment, the inner wall of the tail suspension box is scrubbed by chlorine dioxide disinfectant and 75% alcohol. Fixing the tail of the mouse by using an adhesive tape, hanging the head of the mouse downwards, and recording the accumulated immobility time of the mouse within 5 minutes after the suspension point of the tail of the mouse is 50cm away from the experimental table top after the mouse is adapted for 1 minute.

Results of the experiment

Referring to fig. 1, the forced swimming behavioural results suggest that the immobility time of the 80ng/g fully carboxylated osteocalcin mice was significantly lower than that of the normal control group (p <0.05) compared to the normal saline group. Control group: a physiological saline solution group; group cOCN (8 ng/g): 8ng/g complete carboxylated osteocalcin group; group cOCN (20 ng/g): 20ng/g fully carboxylated osteocalcin group; group cOCN (80 ng/g): 80ng/g of fully carboxylated osteocalcin group; ketamine group. Thus indicating that 80ng/g of fully carboxylated osteocalcin has a rapid antidepressant effect.

Referring to fig. 2, the results of tail suspension experiments suggest that the immobility time of 80ng/g fully carboxylated osteocalcin mice is significantly lower than that of normal control group (p <0.05) compared to normal saline group. Control group: a physiological saline solution group; group cOCN (8 ng/g): 8ng/g complete carboxylated osteocalcin group; group cOCN (20 ng/g): 20ng/g fully carboxylated osteocalcin group; group cOCN (80 ng/g): 80ng/g of fully carboxylated osteocalcin group; ketamine group. Thus indicating that 80ng/g of fully carboxylated osteocalcin has a rapid antidepressant effect.

Claims

1. The application of the fully carboxylated osteocalcin in preparing the antidepressant drug is characterized in that: the dose of the fully carboxylated osteocalcin administered is 80 ng/g.