CN-122005756-A - Application of bacitracin in preparing medicine for treating systemic lupus erythematosus

Abstract

The invention provides an application of gramicidin in preparing medicines for treating systemic lupus erythematosus, wherein the treatment is realized by up-regulating the expression of MTCH 2. The invention verifies the intervention value of the MTCH2 in the systemic lupus erythematosus through experiments, and makes clear that the pontocin can inhibit pathogenic B cell response, restore mitochondrial function and relieve systemic lupus erythematosus disease course through the pharmacological up-regulation of the MTCH2, thereby making up the technical blank of the prior art that the function research of the MTCH2 in autoimmune diseases, especially the systemic lupus erythematosus, is insufficient and lacks the drug application based on the MTCH2 target point.

Inventors

• ZHANG HUI
• WANG MIN
• SUN LINGYUN
• WANG YUZHUO
• ZHANG RUOXUAN

Assignees

• 北京医院

Dates

Publication Date

20260512

Application Date

20260327

Claims (2)

1. 1. Use of bacitracin in the manufacture of a medicament for treating systemic lupus erythematosus.
2. 2. The use according to claim 1, wherein said treatment is effected by up-regulating the expression of MTCH 2.

Description

Application of bacitracin in preparing medicine for treating systemic lupus erythematosus Technical Field The invention belongs to the field of biological medicine, and relates to a medicine for treating systemic lupus erythematosus, in particular to application of bacitracin in preparing a medicine for treating systemic lupus erythematosus. Background Systemic lupus erythematosus (systemic lupus erythematosus, SLE) is an autoimmune disease with complex pathogenesis, characterized by the body producing large amounts of autoantibodies and persistent chronic inflammation, which can cause systemic multiple tissue organ injury. SLE is characterized by the development of immune responses against nuclear autoantigens (e.g., nucleic acids and histones). Furthermore, antibodies can target mitochondria in autoimmune diseases, indicating the interaction between the adaptive immune system and mitochondria. There have been studies reporting a number of pathways leading to SLE pathogenesis due to mitochondrial dysfunction and its secondary oxidative stress. Structural damage and altered function of mitochondria can lead to a variety of pathological states that contribute to the development of SLE, including changes in mitochondrial dynamics, mitochondrial biogenesis and energy metabolism abnormalities, oxidative stress disorders, mitochondrial DNA (mtDNA) damage, and the occurrence of inflammatory responses. Furthermore, mitochondria are involved in cell death pathways including apoptosis, autophagy, necrosis, iron death, and pyro-death, among others, which is another mechanism leading to the appearance of SLE. Mitochondrial carrier homolog 2 (MTCH 2, mitochondrial carrier homolog 2) is a key catalytic enzyme necessary to control the insertion of a variety of protein molecules, including biophysical diversity tail anchor proteins, signal anchor proteins, and multichannel proteins, into the mitochondrial outer membrane. The function of MTCH2 in autoimmune diseases, in particular systemic lupus erythematosus, has not been reported, and specific agonists of MTCH2 have not been reported. The key scientific question of how MTCH2 affects the development of systemic lupus erythematosus is that research is still blank in this field. Disclosure of Invention Aiming at the technical problems in the prior art, the invention provides the application of the gramicidin in preparing the medicines for treating the systemic lupus erythematosus, and the application needs to solve the technical problem that the medicines in the prior art have poor effect in treating the systemic lupus erythematosus. The invention provides application of gramicidin in preparing medicines for treating systemic lupus erythematosus. Further, the treatment is achieved by up-regulating the expression of MTCH 2. According to the invention, a HEK293T cell-based high-throughput screening platform for stably integrating a humanized MTCH2 promoter-EGFP report system is adopted, and the change of the transcriptional activity of the MTCH2 is directly reflected by the change of a fluorescent signal, so that quick, visual and quantifiable screening of an MTCH2 agonist is realized. The invention screens out small molecule candidate bacitracin (GRAMICIDIN) from approved drug library, which can activate MTCH2 transcription stably. The invention verifies the intervention value of the MTCH2 in the systemic lupus erythematosus through experiments, and makes clear that the MTCH2 can inhibit pathogenic B cell response, restore mitochondrial function and relieve systemic lupus erythematosus disease course through pharmacological upregulation, thereby overcoming the technical blank of insufficient functional research of the MTCH2 in autoimmune diseases, especially systemic lupus erythematosus, and lacking the drug application based on the MTCH2 target point in the prior art. Compared with the prior art, the invention has the technical effects of being positive and obvious. The invention discovers that the bacitracin (GRAMICIDIN) can obviously up-regulate the expression of the MTCH2 in primary B cells derived from SLE patients, improve mitochondrial membrane potential and mitochondrial function states, inhibit abnormal activation and oxidative stress of the B cells, and indicate that the bacitracin has molecular targeting effect and can play a role in regulating from the aspects of cellular metabolism and immune function. Compared with the existing treatment strategy aiming at inflammatory reaction or broad immunosuppression, the invention provides a brand new technical approach based on mitochondrial metabolism check point regulation and control, and has the advantages of definite action mechanism and stronger targeting. Meanwhile, the invention provides a new technical means and candidate medicine sources for the research and development of the medicine targeting the mitochondrial inserting enzyme MTCH2, thereby having good social benefit and potential clinical application value.