CN112043696B

CN112043696B - Application of IDO-1 inhibitor in preparation of medicine for treating osteoarthritis

Info

Publication number: CN112043696B
Application number: CN202010881651.1A
Authority: CN
Inventors: 阿哈得; 王大平; 欧阳宏伟; 段莉
Original assignee: Shenzhen Second Peoples Hospital
Current assignee: Shenzhen Second Peoples Hospital
Priority date: 2020-08-26
Filing date: 2020-08-26
Publication date: 2023-02-24
Anticipated expiration: 2040-08-26
Also published as: CN112043696A

Abstract

The invention belongs to the technical field of medicines, and particularly relates to an application of an IDO-1 inhibitor in preparation of a medicine for treating osteoarthritis. According to the invention, rat osteoarthritis is induced through operative meniscus tear, injection containing Epacadostat is injected to the knee joint of a rat suffering from OA, and after two months, the knee joint photos of an experimental group and a control group and dyeing results of HE and toluidine blue show that Epacadostat can effectively prevent cartilage loss and repair cartilage.

Description

Application of IDO-1 inhibitor in preparation of medicine for treating osteoarthritis

Technical Field

The invention belongs to the technical field of medicines, and particularly relates to an application of an IDO-1 inhibitor in preparation of a medicine for treating osteoarthritis.

Background

Osteoarthritis (OA) is a common bone disease characterized by progressive damage of articular cartilage and change of subchondral bone, seriously affects the health and life quality of old people, is one of four major diseases in China, and may become the fourth most serious disease in China by 2020.

The disease is mainly manifested by joint pain, swelling and deformation, and the disease can be caused by degenerative change of cartilage tissue caused by deficiency of nutrients in joint cartilage, extracellular matrix synthesis and degradation disorder and cartilage cell degeneration and necrosis, and finally OA. The current treatment of OA aims to relieve symptoms and improve joint function, and the corresponding treatment measures mainly include oral non-steroidal anti-inflammatory analgesics and advanced artificial joint replacement surgery.

Disclosure of Invention

The invention aims to provide an application of an IDO-1 inhibitor in preparing a medicine for treating osteoarthritis for preparing the medicine for treating osteoarthritis.

Further, IDO-1 inhibitors include Epacadostat.

Another object of the present invention is to provide the use of an IDO-1 inhibitor in a medicament for promoting chondrogenesis.

Further, the IDO-1 inhibitor includes Epacadostat.

According to the invention, rat osteoarthritis is induced through operative meniscus tear, injection containing Epacadostat is injected into the knee joint of a rat suffering from OA for the first time, and after two months, the staining results of knee joint photographs of an experimental group and a control group, HE and toluidine blue show that Epacadostat can effectively reduce cartilage degeneration and enhance cartilage repair.

Drawings

Figure 1 is a graph of the mechanism of action of Epacadostat following intraluminal injection of a drug containing Epacadostat into the knee joint.

Fig. 2 (a) is a photograph of knee joints of rats in an experimental group;

fig. 2 (b) is a photograph of the knee joint of rats of the control group 1;

fig. 2 (c) is a photograph of the knee joint of rats of the control group 2;

FIG. 2 (d) is a photograph of the knee joint of a rat in the sham-operated group;

FIG. 3 is a graph showing the analysis of IDO-1 content in serum of rats in the experimental group, control group 1, control group 2, and sham-operated group.

FIG. 4 shows the percentage of IDO-1 content in the serum of rats in the experimental group, control group 1, control group 2, and sham-operated group.

FIG. 5 (a) is a view showing the histological characteristics of cartilage microscopically obtained by subjecting knee joints of rats in an experimental group to HE staining of a conventional tissue section;

FIG. 5 (b) is a photograph showing the cartilage histology characteristic observed under a microscope by subjecting the knee joint of the rat of the control group 1 to HE staining of a conventional tissue section;

FIG. 5 (c) is a view showing the cartilage histological characteristics under a microscope by performing conventional HE staining of a tissue section of the knee joint of rats in the control group 2;

FIG. 5 (d) shows normal HE staining of tissue sections of the knee joints of the rats in the sham-operated group, and histological characterization of cartilage under a microscope;

FIG. 6 (a) is a toluidine blue staining routine of tissue sections of knee joints of rats in experimental groups, and a cartilaginous histological characteristic map observed under a microscope;

FIG. 6 (b) is a drawing showing the histological characteristics of cartilage microscopically observed by toluidine blue staining of the knee joint of the rat in the control group 1 in a conventional tissue section;

FIG. 6 (c) is a toluidine blue staining routine for tissue sections of knee joints of rats of control group 2, and a cartilaginous histological characteristic diagram is observed under a microscope;

FIG. 6 (d) is a toluidine blue staining of knee joints in the sham-operated group, and a cartilaginous histological characteristic image was observed under a microscope.

Detailed Description

The specific experimental methods and results are as follows:

1. surgical meniscal tear induced osteoarthritis in rats

Wister rats weighing 350g were housed individually in wire cages and in a sanitary ventilated animal room, temperature, humidity and light cycle were all controllable. The food and water can be drunk at will. Animals were acclimated for one week prior to use. Rats were anesthetized with isoflurane and the right knee was scrubbed in preparation for surgery.

Operation group: (1) Connective tissues are cut between the patellar ligament of the knee and the medial collateral ligament, exposing the joint capsule. (2) The joint capsule is incised and the patella dislocated outwardly, exposing the anterior cruciate ligament and severed. (3) The medial meniscal platform ligament is severed and the anterior horn of the medial meniscus is resected. And (4) sewing layer by layer and sterilizing.

The sham operation group: only the skin and the joint cavity are opened, and the incision is flushed by physiological saline and then sutured.

2. Preparation of injection

Epacadostat was dissolved in 0.1% DMSO to obtain an Epacadostat injection.

Dissolving IDO-1 in PBS to obtain IDO-1 injection.

DMSO was dissolved in a neutral PBS solution to obtain a 0.1-% DMSO injection.

3. Establishment of OA animal model

Experimental groups: injecting Epacadostat injection into knee joint of Wister rat in operation group, injecting once every three days, and continuously injecting for two months; the injection metering is as follows: epacadostat in the injected Epacadostat injection solution was 200. Mu.g per 1kg of rat.

Control group 1: injecting IDO-1 injection into knee joint of Wister rat of operation group, injecting once every three days, and continuously injecting for two months; the injection metering is as follows: the amount of IDO-1 in the injected IDO-1 injection per 1kg of rat was 200ng.

Control group 2: the dmso injection solution 0.1% was injected into the knee joint of the Wister rat in the operation group once every three days for two months continuously.

3. Analysis of results

Two months later, the rats of the experimental group, control group 1, control group 2 and sham-operated group were sacrificed, the knee joints were taken out for photographing, HE and toluidine blue staining were performed, and the cartilage histological characteristics were observed under a microscope.

Fig. 2 is a photograph of the joints of rats in the experimental group, the control group 1, the control group 2 and the sham operation group, and it can be seen from the photograph that the appearance of the parent degenerative cartilage, epacadostat and cartilage in the normal group in the IDO-1 group and the DMSO group is good, which indicates that Epacadostat can effectively reduce cartilage degeneration.

It can be seen from FIGS. 3 and 4 that IDO-1 content in the serum of the rats in the experimental group was the lowest; as can be seen from FIG. 2 (b), the high expression of IDO-1 can worsen OA.

From the results of HE staining shown in fig. 5, it can be concluded that Epacadostat can reduce cartilage degeneration by comparing the results of the experimental group with those of the control group 1.

As shown in fig. 6, which shows the result of toluidine blue staining, comparing the results of the experimental group with those of the control group 1, it can be seen that inflammation (indicated by black arrows in the figure) was significantly reduced in the experimental group injected with Epacadostat in the nodal cavity, and at the same time, cartilage repair was enhanced and the number of cartilage was significantly increased as indicated by white arrows in the figure.

While the invention has been described with reference to specific preferred embodiments, it will be understood by those skilled in the art that various changes and modifications may be made without departing from the spirit and scope of the invention as defined in the following claims. Therefore, the protection scope of the present invention shall be subject to the protection scope of the claims.

Claims

Use of an IDO-1 inhibitor, wherein the IDO-1 inhibitor is Epacadostat, in the manufacture of a medicament for the treatment of osteoarthritis.