CN-122017065-A - Application of DHA-RXR-PPAR signal path in promoting postoperative recovery of uterine fibroid after HIFU

Abstract

The invention discloses application of DHA-RXR-PPAR signal path in promoting postoperative recovery of uterine fibroid after HIFU. According to the invention, through the combination of clinical sample metabolic spectrum analysis and in-vitro cell function experiments, research proves that the differential metabolite DHA drives macrophage metabolism reprogramming through the RXR-PPAR signal shaft, so that the differential metabolite DHA is promoted to be transformed into an anti-inflammatory and phagocytosis-promoting repair type phenotype, the absorption and repair process of uterine fibroids after HIFU operation is accelerated, and a new intervention target (RXR-PPARgamma shaft) and a potential new medicament are provided for HIFU operation.

Inventors

• HAN DINGLI
• ZHANG JIA
• LIANG SHUANG

Assignees

• 重庆医科大学

Dates

Publication Date

20260512

Application Date

20260130

Claims (10)

1. Application of DHA-RXR-PPAR signal path as target in screening medicine for promoting postoperative recovery of hysteromyoma after HIFU.
2. 2. The method of claim 1, wherein the agent upregulates DHA levels in the subject following HIFU from uterine fibroids.
3. 3. The method of claim 1, wherein the agent upregulates the expression levels of PPARgamma and RXRalpha in macrophages, promotes phagocytosis, and promotes uterine fibroids reduction and postoperative recovery.
4. 4. The method according to claim 1, wherein DHA mediates the energy metabolism of macrophages via RXR-PPAR signal pathways, thereby affecting the functional status thereof.
5. 5. The method of claim 1, wherein DHA drives the metabolic reprogramming of macrophages via RXR-PPAR signal axes, thereby promoting the transformation of macrophages into an anti-inflammatory, phagocytic repair phenotype, and accelerating the absorption and repair process of uterine fibroids after HIFU surgery.
6. Use of an accelerator of the dha-RXR-PPAR signaling pathway in the preparation of a product for promoting post-operative recovery of uterine fibroids HIFU.
7. 7. The method of claim 6, wherein the method comprises the step of driving the metabolic reprogramming of the postoperative macrophages of the uterine fibroids after HIFU through the promoter of the DHA-RXR-PPAR signal pathway, thereby promoting the transformation of the uterine fibroids to an anti-inflammatory and phagocytic repair type phenotype and accelerating the absorption and repair process of the uterine fibroids after HIFU operation.
8. 8. The method according to claim 6, wherein the promoter of the DHA-RXR-PPAR signal pathway is any of the following: (1) An accelerator of DHA; (2) An accelerator of RXR; (3) An accelerator of PPAR; (4) Promoters of the RXR-PPAR signaling pathway.
9. 9. Use of docosahexaenoic acid in the manufacture of a medicament for promoting postoperative recovery of uterine fibroids after HIFU.
10. 10. Use of a biological material comprising docosahexaenoic acid or a substance that promotes expression of docosahexaenoic acid in a subject in the manufacture of a medicament for promoting post-operative recovery of uterine fibroids HIFU.

Description

Application of DHA-RXR-PPAR signal path in promoting postoperative recovery of uterine fibroid after HIFU Technical Field The invention belongs to the technical field of biological medicines, and relates to application of a DHA-RXR-PPAR signal path in promoting postoperative recovery of uterine fibroid after HIFU. Background Hysteromyoma is the most common pelvic benign tumor in women. Uterine leiomyomas have a high incidence of up to 70% in perimenopausal women. Uterine fibroids are considered to be a typical fibrotic disease, although the etiology is not yet defined, and there is a model that indicates that myoma formation may be the result of excessive wound healing, which is driven by a deregulation of the inflammatory process. High intensity focused ultrasound, HIFU, is a non-invasive local treatment technique. The principle is that ultrasonic energy emitted from outside body is concentrated on focus to produce irreversible coagulation necrosis, and heat, mechanical and cavitation effect is utilized to inactivate tumor tissue. The HIFU provides a safer and more effective treatment scheme for patients with uterine fibroids, has the characteristics of no invasiveness, no scar, repeatable treatment, no radiation, one-time full-coverage accurate thermal ablation, fewer complications, short time and the like, has no obvious influence on endocrine function of ovaries, and has wider clinical application of the HIFU tumor ablation. The research shows that after the HIFU ablates the tumor, the very obvious immune inflammatory reaction related to ablation can be generated, which is expressed as infiltration of immune cells around the ablation focus, and the research monitors that the organism endothelin, endorphin and prostaglandin have obvious metabolic changes after the HIFU operation, which indicates that the HIFU treatment has influence on in vivo inflammation and steady state regulation. The inflammatory reaction after ablation is a dynamic change process, and along with the start of the clearing and repairing process of necrotic tissues, the inflammatory reaction gradually weakens and tends to be stable, thereby laying a good foundation for the comprehensive recovery of the organism. Following HIFU ablation, necrotic tissue can induce infiltration and activation of a large number of immune cells, particularly macrophages. Macrophages, a key member of the innate immune system, are highly plastic and can be polarized under different signal stimuli to pro-inflammatory M1-type or anti-inflammatory repair M2-type subpopulations. Studies have shown that endogenous signals released by necrotic tissue induce macrophage activation, polarization and metabolic remodeling. In particular, M2-type macrophages play an important role in tissue repair, inflammation inhibition and focal clearance, the function of which depends on the enhancement of fatty acid oxidation and mitochondrial metabolism. Metabolic reprogramming has received widespread attention in recent years as a key mechanism for macrophage phenotype transformation. Peroxisome Proliferator Activated Receptors (PPARs) are members of the nuclear hormone receptor superfamily, comprising three subtypes PPARα, PPARβ/δ and PPARγ, and regulate transcription through PPAR response elements (PPRE) that form heterodimers with the Retinoid X Receptor (RXR) binding target genes. PPARgamma is an important transcription factor for regulating fatty acid metabolism and oxidative phosphorylation, and can promote M2 type polarization, and RXR (retinoic acid X receptor) is used as a heterodimer binding partner thereof, and together with PPARgamma, can regulate the expression of downstream target genes, so as to form RXR-PPAR signal axis. It has been demonstrated that activating this pathway not only enhances fatty acid uptake and oxidation, but also drives the shift of glycolysis to aerobic metabolism, thereby inducing macrophage transformation to the M2 phenotype. Disclosure of Invention The invention aims at solving the problems and provides an application of a DHA-RXR-PPAR signal path in promoting postoperative recovery of uterine fibroid after HIFU. In order to achieve the purpose, the invention adopts the following technical scheme: The first aspect of the invention provides the use of a DHA-RXR-PPAR signaling pathway as a target in the screening of a drug that promotes post-operative recovery of uterine fibroids after HIFU. In the above application technical scheme, the medicament regulates the DHA level of the subject after the uterine fibroid HIFU. In the application technical scheme, the medicament can up-regulate the expression level of PPARgamma and RXR alpha of macrophages, promote phagocytic function of the macrophages and promote shrinkage and postoperative recovery of hysteromyoma. In the application technical scheme, DHA mediates energy metabolism regulation of macrophages through RXR-PPAR signal paths, and further influences the functional state of the macrophage