阅读说明：本技术 pifithrin-μ在制备放疗辐照后促进皮肤伤口愈合的药物中的应用 (Application of pifithrin-mu in preparation of medicine for promoting skin wound healing after radiotherapy irradiation ) 是由 孙鹏 张亮 王国栋 赵云富 朱培英 林德锋 于 2019-09-18 设计创作，主要内容包括：本发明涉及医药技术领域,具体是p53抑制剂pifithrin-μ在制备放疗辐照后促进皮肤伤口愈合的药物中的应用。本发明提供了p53抑制剂pifithrin-μ的一种新的应用,其可以恢复辐照后小鼠胚胎成纤维细胞增殖,减少辐照细胞凋亡,促进辐照后皮肤伤口的愈合,这对辐照后皮肤伤口的愈合具有重大意义；pifithrin-μ是可以人工合成的一种生物小分子,因此成本低廉,可以大量生产。(The invention relates to the technical field of medicines, in particular to application of a p53 inhibitor pifithrin-mu in preparation of a medicine for promoting skin wound healing after radiotherapy irradiation. The invention provides a new application of a p53 inhibitor pifithrin-mu, which can recover mouse embryo fibroblast proliferation after irradiation, reduce irradiation cell apoptosis and promote the healing of skin wounds after irradiation, and has great significance for the healing of skin wounds after irradiation; the pifithrin-mu is a biological small molecule which can be artificially synthesized, so the cost is low and the pifithrin-mu can be produced in large quantities.)

Application of pifithrin-mu in preparation of medicines for promoting skin wound healing after radiotherapy irradiation.

2. Pifithrin-mu according to claim 1 in the preparation of a medicament for promoting healing of skin wounds following radiation therapy irradiationThe application of (A), wherein the radiotherapy irradiation is Co⁶⁰And (4) irradiating gamma rays.

Application of pifithrin-mu in preparation of medicine or reagent for promoting skin fibroblast proliferation after radiotherapy irradiation.

4. Use of pifithrin-mu according to claim 3 in the preparation of a medicament or agent for promoting proliferation of dermal fibroblasts following radiation therapy irradiation with Co⁶⁰And (4) irradiating gamma rays.

5. A pharmaceutical preparation for promoting skin wound healing after radiotherapy irradiation contains pifithrin-mu as active ingredient.

6. The pharmaceutical formulation of claim 5, wherein said radiation therapy radiation is Co⁶⁰And (4) irradiating gamma rays.

7. The pharmaceutical preparation of claim 5, wherein the pharmaceutical preparation for promoting skin wound healing after radiation treatment further comprises a pharmaceutically acceptable carrier or adjuvant.

Technical Field

The invention relates to the technical field of medicines, in particular to application of a p53 inhibitor pifithrin-mu in preparing a medicine for promoting skin wound healing after radiotherapy irradiation.

Background

Radiotherapy is a therapeutic method for killing tumor cells by using the effect of Ionizing Radiation (IR), and plays an important role in the treatment of head and neck malignant tumors. According to literature statistics, about 5492200 new head and neck cancer cases are increased every year worldwide, and more than 50% of patients need to receive radiotherapy during the treatment process. Clinically, besides the therapeutic effect of radiotherapy, the frequently-induced complications are acute skin damage (mainly manifested by erythema, desquamation, hair loss, ulcer and the like) and skin wound healing disorder after surgical operation. The latter is mainly manifested by delayed healing, disunion or repeated ulceration of the local operation wound, increasing the probability of infection and tissue necrosis at the wound site, and finally turning into radiation skin ulcer.

pifithrin- μ inhibits the binding of p53 to mitochondria by decreasing the affinity of p53 to the anti-apoptotic proteins Bcl-xL and Bcl-2. pifithrin- μ is highly specific for p53 and does not protect cells from apoptosis due to overexpression of the apoptosis precursor protein Bax or the use of dexamethasone. pifithrin-. mu.s are able to rescue radiation-induced P53-mediated apoptosis of the thymocytes of naive mice and protect mice from radiation-induced fatal hematopoietic syndrome (STROM E, SATHES, KOMAROV P G, et. Small-molecule inhibitor of P53binding to mitochondria protects microorganism gamma irradiation [ J ]. Nat Chem Biol,2006.2(9):474-9. doi: 10.1038/nchemmbio 809).

At present, no report exists on the application of the p53 inhibitor pifithrin-mu in skin wound healing after irradiation.

Disclosure of Invention

The invention aims to provide a new application of a p53 inhibitor pifithrin-mu.

In a first aspect of the invention, there is provided the use of pifithrin-mu in the manufacture of a medicament for promoting healing of a skin wound following radiation treatment irradiation.

Through a large number of experimental researches, the present invention surprisingly discovers that pifithrin-mu has the effect of accelerating the recovery of the skin wound after irradiation.

The in vivo experiment proves that the pifithrin-mu can accelerate the proliferation of long-term passage cells after irradiation after blocking a p53 channel, and has no influence on the proliferation of normal cells.

In the present invention, the pifithrin-mu is a small biological molecule that can be artificially synthesized, and is commercially available from sigma or seleck.

Further, the radiotherapy irradiation of the cells is Co⁶⁰Gamma ray irradiation; the total radiation dose is 10Gy, and the radiation irradiation of the mice is Co⁶⁰gamma ray irradiation; the total radiation dose was 5 Gy.

In a second aspect of the invention, there is provided the use of pifithrin-mu in the preparation of a medicament or agent for promoting proliferation of dermal fibroblasts following radiation treatment irradiation.

In a third aspect of the present invention, there is provided a pharmaceutical preparation for promoting the healing of skin wounds after irradiation with radiation therapy, which comprises pifithrin- μ as an active ingredient.

Furthermore, the pharmaceutical preparation for promoting skin wound healing after radiotherapy irradiation also comprises a pharmaceutically acceptable carrier or auxiliary material.

The invention has the advantages that:

1. The invention provides a new application of p53 inhibitor pifithrin-mu, which can effectively promote the healing of skin wounds after irradiation. The method has great significance for healing of skin wounds after irradiation;

2. The pifithrin-mu is a biological small molecule which can be artificially synthesized, so the cost is low and the pifithrin-mu can be produced in large quantities.

Drawings

FIG. 1 is a photograph of the p53 inhibitor pifithrin-mu promoting proliferation of dermal fibroblasts in mice after long-term passage after irradiation. A picture shows that the content of p53 pathway downstream protein p21 is obviously reduced after the p53 inhibitor pifithrin-mu acts, which indicates that the p53 inhibitor pifithrin-mu acts well; b is a p21 protein expression quantitative result after p53 inhibitor pifithrin-mu acts; and the C picture shows that the cell proliferation rate of the 3 rd generation mouse embryo fibroblast is 1 day (24h) after the P53 inhibitor pifithrin-mu is irradiated, and the cell proliferation rate of the pifithrin-mu action group is obviously changed compared with that of a control group (P is less than 0.05).

FIG. 2. A: the wound was photographed at each time point and the results were obtained; b: and comparing the results of the histogram of the wound area at each time point.

Detailed Description

The following detailed description of the present invention will be made with reference to the accompanying drawings.

The experimental procedures, for which specific conditions are not noted in the following examples, are generally carried out under conventional conditions, or under conditions recommended by the manufacturer.