Application of resolvin E1 in preparation of medicine for relieving pulpitis and / or promoting damage repair of dental pulp tissue

Abstract

The invention provides application of resolvin E1 in preparation of a medicine for relieving pulpitis and / or promoting repair of dental pulp tissue damage. According to the application, pulpitis can be effectively improved, the pulp retention rate is increased, and a new thought is provided for development, screening and preparation of drugs for relieving pulpitis and / or promoting damage repair of dental pulp tissues.

Description

Technical Field

[0001] The present invention belongs to the field of biomedicine technology, and specifically relates to the use of resolvin E1 in the preparation of a medicine for alleviating pulpitis and / or promoting the repair of pulp tissue damage. Background Art

[0002] Dental health problems are quite common around the world. According to data, more than 2 billion people suffer from dental caries in permanent teeth, accounting for about 36% of the total population. At the same time, about 600 million children suffer from dental caries in deciduous teeth, accounting for about 9% of the total population. These untreated deep caries can gradually develop from enamel to dentin and eventually involve pulp tissue, causing pulp inflammation or infection. The treatment of permanent dental pulp infection in children and adolescents remains a major challenge in the field of dentistry.

[0003] Conventional pulpectomy or root canal treatment can control infection in the short term, but it may be accompanied by postoperative pain, periapical lesions caused by microleakage of the crown, and root fractures, which increase the risk of tooth extraction in the future. However, histological observations revealed that even in cases diagnosed as irreversible pulpitis, the pulp tissue did not show severe damage, only inflammatory cell infiltration or local necrosis of the coronal pulp. This study suggests that the pulp still has the potential for repair under inflammatory conditions.

[0004] Human dental pulp stem cells (DPSCs) are considered to be neural crest stem cells / progenitor cells retained in the dental pulp. They have the ability of self-renewal and multipotent differentiation, and can differentiate into a variety of cell types including odontoblasts, adipocytes, fibroblasts and epithelial cells. At the same time, these cells can promote the repair and regeneration of the dental pulp by inhibiting immune responses and regulating the secretion of inflammatory factors. The final result of dental pulp damage lies in the balance between inflammation and repair. Studies have shown that inflammation resolution is not a purely passive process, but an active, programmed response. Moderate inflammatory responses can initiate the migration, proliferation and differentiation of DPSCs, thereby promoting tissue regeneration. Conversely, excessive inflammation leads to pulp necrosis. Summary of the invention

[0005] The present invention aims to provide the use of resolvin E1 in the preparation of a medicine for alleviating pulpitis and / or promoting the repair of pulp tissue damage.

[0006] The first invention of the present invention provides the use of resolvin E1 in the preparation of a drug for alleviating pulpitis and / or promoting the repair of pulp tissue damage.

[0007] In one embodiment, the resolvin E1 is formulated in a pharmaceutically acceptable carrier.

[0008] In one embodiment, resolvin E1 is used as an active ingredient in the preparation of a drug for alleviating pulpitis and / or promoting the repair of pulp tissue damage.

[0009] The second invention of the present invention provides a medicine, comprising resolvin E1.

[0010] In one embodiment, the drug is a drug for alleviating pulpitis.

[0011] In one embodiment, the drug is a drug for promoting the repair of dental pulp tissue damage.

[0012] In one embodiment, the drug is a drug for alleviating pulpitis and promoting the repair of pulp tissue damage.

[0013] In one embodiment, the invention further comprises a pharmaceutically acceptable carrier of resolvin E1.

[0014] In one embodiment, the pharmaceutically acceptable carrier is a diluent, a disintegrant, a binder, a lubricant, a stabilizer or a corrigent.

[0015] In one embodiment, the drug contains resolvin E1 as an active ingredient.

[0016] Compared with the prior art, the beneficial effects of the present invention are as follows: the use of the resolvin E1 provided by the present invention in the preparation of a drug for alleviating pulpitis and / or promoting the repair of pulp tissue damage. This use can effectively improve pulp inflammation and improve the pulp preservation rate, and provides a new idea for the development, screening and preparation of drugs for alleviating pulpitis and / or promoting the repair of pulp tissue damage.

[0017] In the application of the resolvin E1 provided by the present invention in the preparation of a drug for alleviating pulpitis and / or promoting the repair of pulp tissue damage, RvE1 reverses the effect of TNF-α, can upregulate the expression of DMP1, SCP1, ALP, ON and OCN, significantly downregulate the expression of inflammatory markers such as IL-4, IL-6 and IL-1β, and significantly upregulates the levels of metabolites such as adenosine, thereby realizing the application of RvE1 in the preparation of a drug for alleviating pulpitis and / or promoting the repair of pulp tissue damage. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 This is the result of the expression of dentin marker ALP after DPSCs were stimulated by TNF-α and then stimulated by RvE1;

[0019] Figure 2 This is the result of inflammatory marker IL-6 expression after DPSCs were stimulated by TNF-α and then stimulated by RvE1;

[0020] Figure 3 This is the result of full-spectrum metabolomics detection of RvE1 upregulating the expression of adenosine metabolites in DPSCs. DETAILED DESCRIPTION

[0021] In this article, the range expressed by "a value to another value" is a summary expression method to avoid listing all the values ​​in the range one by one in the specification. Therefore, the description of a specific numerical range covers any value in the numerical range and a smaller numerical range defined by any value in the numerical range, just as if the arbitrary value and the smaller numerical range were explicitly written in the specification.

[0022] In this application, the use of "or" means "and / or" unless otherwise stated. In the case of multiple dependent claims, use of "or" refers to more than one of the preceding independent or dependent claims only in the alternative.

[0023] Unless otherwise stated, the experimental methods, detection methods, and preparation methods disclosed in the present invention all adopt conventional techniques in the field of molecular biology, biochemistry, chromatin structure and analysis, analytical chemistry, cell culture, recombinant DNA technology, and related fields.

[0024] The resolvin family is a new type of endogenous pro-inflammatory resolution mediator discovered in recent years. Among them, resolvin E1 (RvE1) has shown good anti-inflammatory effects in a variety of inflammatory diseases. RvE1 can inhibit the expression of pro-inflammatory cytokines and the transendothelial migration of neutrophils, preventing tissue damage caused by inflammation. In the experimental model of periodontitis, RvE1 has been shown to promote periodontal regeneration and induce the formation of alveolar bone and cementum. In addition, RvE1 has shown protective effects on periodontal diseases in rabbits, colitis, peritonitis and acute lung injury in mice, and can directly affect tendon matrix cells and promote the resolution of inflammation in periarticular tendinitis.

[0025] Although resolvin E1 has shown a wide range of effects in other tissues and disease models, there is currently no research to clarify its role in pulp tissue. The present invention studies whether RvE1 can promote pulp tissue damage and regeneration by mobilizing DPSCs to proliferate and differentiate and regulating inflammation resolution. The present invention proposes that resolvin E1 (RvE1) may be used to improve the state of clinical pulp inflammation and promote pulp tissue repair. The currently commonly used technology mainly relies on sodium hypochlorite and saline to rinse the inflammatory pulp tissue, but its reversal effect on pulp inflammation is controversial, and the success rate is difficult to guarantee. The combined use of resolvin E1 and adenosine may provide a convenient way to effectively improve pulp inflammation and increase pulp preservation rate. This discovery provides a new perspective and method for the clinical treatment of pulp inflammation, which has important research and application value.

[0026] The present invention is further described below by means of specific examples.

[0027] Example 1

[0028] In this example, an experiment was conducted to verify the use of resolvin E1 in the preparation of a drug for alleviating pulpitis and / or promoting the repair of pulp tissue damage.

[0029] The experimental steps are as follows:

[0030] (1) Isolation and culture of DPSCs in human dental pulp tissue: Fresh supernumerary teeth that need to be extracted were selected from the patients, the dental pulp was isolated, and the pulp tissue was cut into small pieces. The DPSCs were isolated and cultured using the tissue block enzymatic digestion method. The DPSCs were cultured in maintenance medium (MM) containing nucleosides, 10% FBS, and 1% penicillin-streptomycin (PS). The experiment started with P3 cells.

[0031] (2) Detection of the effect of RvE1 on the proliferation of DPSCs under inflammatory conditions: After DPSCs were stimulated with 0 ng / mL and 50 ng / mL TNF-α, 100 nM RvE1 was added or not added to the culture medium.

[0032] (3) Detection of the effect of RvE1 on odontoblast differentiation of DPSCs under inflammatory conditions: After DPSCs were stimulated with 0 and 50 ng / mL TNF-α, 100 nM RvE1 was added or not added to the culture medium. The expression of DPSCs dentin markers DMP1, SCP1, ALP, ON and OCN was detected by PCR. The results showed that after TNF-α stimulation of DPSCs, the expression of DMP1, SCP1, ALP, ON and OCN was significantly decreased, while RvE1 reversed the effect of TNF-α and upregulated the expression of these markers, such as Figure 1 shown.

[0033] (4) Detection of the effect of RvE1 on inflammatory markers of DPSCs under inflammatory conditions: After stimulating DPSCs with 0 and 50 ng / mL TNF-α, 100 nM RvE1 was added or not added to the culture medium, and the expression of inflammatory markers IL-4, IL-6 and IL-1β of DPSCs was detected by PCR experiments. The results showed that after TNF-α stimulated DPSCs, the expression of cell inflammatory markers increased significantly, while RvE1 reversed the pro-inflammatory effect of TNF-α and significantly downregulated the expression of inflammatory markers such as IL-4, IL-6 and IL-1β. The results are shown in Figure 2. Figure 2 shown.

[0034] (5) Detection of the effect of RvE1 on the metabolic level of DPSCs: DPSCs were stimulated with 0 and 100 nM RvE1, metabolites were extracted and concentrated, and the effect of RvE1 on DPSCs metabolites was detected by full-spectrum metabolomics. The results showed that the levels of metabolites such as adenosine were significantly upregulated, such as Figure 3 shown.

[0035] Test results:

[0036] The results showed that RvE1 could promote the proliferation potential and odontoblast differentiation of DPSCs under inflammatory conditions and inhibit the expression of inflammatory markers, such as Figure 1 , Figure 2 As shown in Figure 2, the degree of odontoblast differentiation represents the ability of dental pulp to repair damage. The stronger the odontoblast differentiation, the better the repair ability of dental pulp tissue.

[0037] The effect of RvE1 on DPSCs metabolites was detected by full-spectrum metabolomics. The results showed that after RvE1 stimulation, the purine metabolism level increased significantly, among which adenosine expression was significantly increased, such as Figure 3 shown.

[0038] After TNF-α stimulated DPSCs, RvE1 was added or not added to the culture medium, and the expression of adenosine in DPSCs was detected. The results showed that after TNF-α stimulation, the expression level of adenosine in DPSCs decreased, and RvE1 stimulation reversed the decrease in the expression level of adenosine under inflammatory state.

[0039] In summary, the above results indicate that RvE1 promotes the repair of dental pulp tissue damage by increasing the expression of adenosine in DPSCs under inflammatory conditions.

[0040] The above disclosure is only the preferred embodiment of the present invention. The preferred embodiment does not describe all the details in detail, nor does it limit the invention to the specific implementation method described. Obviously, many modifications and changes can be made according to the content of this specification. This specification selects and specifically describes these embodiments in order to better explain the principles and practical applications of the present invention, so that those skilled in the art can make good use of the present invention. The present invention is limited only by the claims and their full scope and equivalents.

[0041] Under the guidance of the present invention and the above-mentioned embodiments, it is easy for those skilled in the art to foresee that each raw material or its equivalent substitute, each processing method or its equivalent substitute listed or exemplified in the present invention can realize the present invention, and the upper and lower limit values ​​and interval values ​​of the parameters of each raw material and processing method can realize the present invention, and the embodiments are not listed one by one here.

Claims

1. Use of resolvin E1 in the preparation of a drug for alleviating pulpitis and / or promoting the repair of pulp tissue damage.

2. The use according to claim 1, characterized in that: The resolvin E1 is formulated in a pharmaceutically acceptable carrier.

3. The use according to claim 1, characterized in that: A drug for relieving pulpitis and / or promoting the repair of pulp tissue damage is prepared with resolvin E1 as the active ingredient.

4. A drug, characterized in that Including resolvin E1.

5. The drug according to claim 4, characterized in that The medicine is a medicine for alleviating pulpitis.

6. The drug according to claim 4, characterized in that The medicine is used for promoting the repair of dental pulp tissue damage.

7. The drug according to claim 4, characterized in that The medicine is used for alleviating pulpitis and promoting the repair of pulp tissue damage.

8. The drug according to claim 4, characterized in that The invention also comprises a pharmaceutically acceptable carrier of resolvin E1.

9. The drug according to claim 8, characterized in that The pharmaceutically acceptable carrier is a diluent, a disintegrant, a binder, a lubricant, a stabilizer or a corrective agent.

10. The drug according to claim 4, characterized in that The drug uses resolvin E1 as an active ingredient.

Images