CN-121987655-A - Application of k-252a in preparation of medicines for inhibiting pulmonary fibrosis

Abstract

The invention discloses an application of k-252a in preparing a medicine for inhibiting pulmonary fibrosis, and belongs to the technical field of clinical medicine. The k-252a is an inhibitor of nerve growth factor NGF, and the nerve growth factor NGF can obviously enhance the differentiation of lung fibroblast MRC5 cells, and the induction and differentiation are accompanied with the increase of the expression of a receptor TrkA, so that the migration capacity and the activation capacity of the lung fibroblast cells are obviously enhanced. The k-252a of the invention can inhibit the protein expression of TGF-beta 1 and immune response factors IL-2RA and IFN-gamma caused by nerve growth factor NGF, thereby achieving the purpose of inhibiting pulmonary fibrosis, especially idiopathic pulmonary fibrosis.

Inventors

• ZHU HONGLAN
• ZHOU AIMING
• Ran Xingfen
• HE RUNRUN

Assignees

• 贵州省人民医院

Dates

Publication Date

20260508

Application Date

20260212

Claims (6)

1. Use of 1.k-252a in the manufacture of a medicament for inhibiting pulmonary fibrosis.
2. 2. The method according to claim 1, wherein the pulmonary fibrosis is selected from the group consisting of primary pulmonary fibrosis, secondary pulmonary fibrosis, idiopathic pulmonary fibrosis, interstitial pulmonary fibrosis and interstitial pneumonia.
3. 3. The method according to claim 1, wherein the pulmonary fibrosis is idiopathic pulmonary fibrosis.
4. 4. A drug for inhibiting pulmonary fibrosis is characterized by comprising k-252a and a pharmaceutically acceptable carrier or excipient.
5. 5. The agent for inhibiting pulmonary fibrosis according to claim 4, wherein the k-252a is contained in an amount of 0.1mg-500mg per unit dose.
6. 6. The pharmaceutical composition for inhibiting pulmonary fibrosis according to claim 4, wherein the pharmaceutical composition comprises an oral dosage form and/or a non-oral dosage form, wherein the oral dosage form comprises any one or more of a capsule, a tablet and an oral liquid, and wherein the non-oral dosage form comprises an aerosol or dry powder inhalant, or an injection, suitable for inhalation.

Description

Application of k-252a in preparation of medicines for inhibiting pulmonary fibrosis Technical Field The invention relates to the technical field of clinical medicine, in particular to application of k-252a in preparation of a medicine for inhibiting pulmonary fibrosis. Background Idiopathic Pulmonary Fibrosis (IPF) is a chronic and progressive pulmonary disease affecting interstitial tissue, which is characterized by the usual interstitial pneumonia found by high resolution computed tomography or biopsy, but the specific etiology is currently unknown. The incidence of IPF has increased year by year in recent years. The treatment means are limited, and the medicines approved at present for treating pulmonary fibrosis can only delay the progress of the illness. Therefore, the active search for the medicines for treating pulmonary fibrosis is urgent. Disclosure of Invention The invention provides an application of k-252a in preparing a medicine for inhibiting pulmonary fibrosis. In order to achieve the above object, the present invention is achieved by the following technical scheme: The first object of the invention is to provide an application of a nerve growth factor NGF inhibitor k-252a in preparing a medicine for inhibiting pulmonary fibrosis. Further, the pulmonary fibrosis comprises one or more of primary pulmonary fibrosis, secondary pulmonary fibrosis, idiopathic pulmonary fibrosis, pulmonary interstitial fibrosis and interstitial pneumonia. Preferably, the pulmonary fibrosis is idiopathic pulmonary fibrosis. A second object of the present invention is to provide a medicament for inhibiting pulmonary fibrosis. Further, the medicament comprises k-252a and a pharmaceutically acceptable carrier or excipient. Further, the content of k-252a in the medicine is 0.1mg-500mg per unit dose. Further, the dosage forms of the medicine comprise oral dosage forms and/or non-oral dosage forms, wherein the oral dosage forms comprise any one or more of capsules, tablets or oral liquid, and the non-oral dosage forms comprise atomized liquid or dry powder inhalants or injections which are suitable for inhalation administration. The application of the k-252a in preparing the medicine for inhibiting the pulmonary fibrosis has the following beneficial effects: The k-252a is an inhibitor of nerve growth factor NGF, and the nerve growth factor NGF can obviously enhance the differentiation of lung fibroblast MRC5 cells, and the induction and differentiation are accompanied with the increase of the expression of a receptor TrkA, so that the migration capacity and the activation capacity of the lung fibroblast cells are obviously enhanced. The k-252a of the invention can inhibit the protein expression of TGF-beta 1 and immune response factors IL-2RA and IFN-gamma caused by nerve growth factor NGF, thereby achieving the purpose of inhibiting pulmonary fibrosis, especially idiopathic pulmonary fibrosis. Drawings In order to more clearly illustrate the embodiments of the invention or the technical solutions of the prior art, the drawings which are used in the description of the embodiments or the prior art will be briefly described, it being obvious that the drawings in the description below are only some embodiments of the invention, and that other drawings can be obtained according to these drawings without inventive faculty for a person skilled in the art. FIG. 1 is a schematic diagram showing the result of inhibiting human lung fibroblast activation by inhibiting TrkA/FAK/ERK signal pathway, wherein A is CCK8 to detect the influence of k-252a on MRC5 cell proliferation, B is RT-qPCR to detect the influence of k-252a on mRNA level expression of the differentiation markers ACTA2, COL1A1 and FN1, C and D are WB to detect the influence of k-252a on protein expression levels of the differentiation markers alpha-SMA, collagen I and fibrafectin 1, E is scratch test to detect the influence of k-252a on MRC5 cell migration ability, F is Transwell to detect the influence of k-252a on MRC5 cell migration ability, G and H are WB to detect the influence of k-252a on NGF, p75NTR, trkA, p-FAK and p-ERK expression. FIG. 2 is a schematic diagram showing the result of inhibiting the formation of pulmonary fibrosis of a mouse by the drug k-252a of the invention, wherein A is RT-qPCR for detecting mRNA level expression of fibrosis markers acta, col1a1 and fn1 in the pulmonary tissue of the mouse, B is a schematic diagram of HE staining of the pulmonary tissue, C is a scheme for evaluating the pulmonary fibrosis degree of the mouse by Ashcroft scoring, D is a schematic diagram of Masson staining of the pulmonary tissue, E is a result of hydroxyproline detection on the pulmonary tissue of the mouse, F is a protein expression level of alpha-SMA in the pulmonary tissue of the mouse, G is a protein expression level of Collagen I in the pulmonary tissue of the mouse by immunohistochemical detection. FIG. 3 is a schematic diagram showing the results of i