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Glycolysis inhibitor and application thereof to repair of damage of endothelial cells

A glycolysis and cell technology, applied in the repair of endothelial cell damage, in the field of glycolysis inhibitors, to reduce the risk of treatment failure, improve prognosis, and reduce mortality

Active Publication Date: 2020-11-27
PEOPLES HOSPITAL PEKING UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

There is no effective treatment for patients with hematopoietic suppression after chemotherapy and implantation dysfunction after transplantation, and only symptomatic treatment can be performed by infusion of growth factors and blood products.

Method used

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  • Glycolysis inhibitor and application thereof to repair of damage of endothelial cells
  • Glycolysis inhibitor and application thereof to repair of damage of endothelial cells
  • Glycolysis inhibitor and application thereof to repair of damage of endothelial cells

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0060] Example 1: Detecting the expression of glycolysis-related proteins in bone marrow vascular endothelial cells of patients with poor engraftment function after transplantation

[0061] In order to verify whether abnormal glycolysis is involved in the occurrence of poor engraftment after transplantation, this study used flow sorting ( figure 1 A) Transcriptome sequencing analysis of bone marrow vascular endothelial cells in patients with poor engraftment function and good engraftment function after transplantation combined with micro-library construction. The results showed that, compared with patients with good engraftment function after transplantation, glycolysis-related genes (such as SLC2A3 , HK1, HK2, HK3, PFKFB2, PFKFB3, PFKFB4, etc.) were significantly increased in bone marrow endothelial cells of patients with poor engraftment after transplantation ( figure 1 B). Subsequently, the inventors conducted a prospective clinical paired study to measure the protein expr...

Embodiment 2

[0062] Example 2: In vitro experiments show abnormal glycolysis in damaged bone marrow vascular endothelial cells

[0063] In order to further study the changes of function and glycolysis level of human bone marrow vascular endothelial cells before and after injury, the present inventors constructed an in vitro injury model of human bone marrow vascular endothelial cells by treating with chemotherapeutic drug 5-FU. The inventor's experiments found that after the chemotherapeutic drug 5-FU was processed, the cell number of human bone marrow vascular endothelial cells was significantly reduced ( figure 2 A), significantly increased apoptosis ( figure 2 B and 2C), the migration ability was weakened ( figure 2 D). Simultaneously, the inventor also found that the consumption of glucose in injured human bone marrow vascular endothelial cells ( figure 2 E) and lactic acid production ( figure 2 F) Significantly increased and increased expression of glycolysis-related genes (g...

Embodiment 3

[0064] Example 3: In vitro experiments show that glycolysis inhibitors can reduce the damage of human bone marrow vascular endothelial cells

[0065] Glycolysis inhibitor 3PO (10μM) can reduce the abnormally increased sugar consumption and lactic acid production of bone marrow vascular endothelial cells caused by chemotherapeutics (5-FU) treatment injury ( image 3 A and 3B) to restore it to the level close to that of the (dimethyl sulfoxide) group (control group, also denoted as CTL group). In addition, the number of cells in the 3PO treatment group was significantly increased compared with the 5-FU group ( image 3 C). At the same time, compared with the 5-FU group, the apoptotic ratio of bone marrow vascular endothelial cells was significantly reduced in the 3PO group ( image 3 D). Moreover, compared with the 5-FU group, the migration ability of the 3PO group was significantly increased ( image 3 E).

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Abstract

The invention provides a reagent kit for detecting the condition of vascular endothelial cells, a medicine for treating abnormality of the vascular endothelial cells, and a reagent kit which is used for treating diseases relevant to the vascular endothelial cells and includes a glycolysis inhibitor medicine and other medicines for treating the diseases relevant to the vascular endothelial cells. The invention also provides an application of a PFKFB3 enzyme detection reagent to detection of the condition of the vascular endothelial cells and an application of a glycolysis inhibitor to preparation of medicines or reagent kits for treating the abnormality of the vascular endothelial cells of an examinee. The health status or the prognosis prospects can be judged according to the state of thevascular endothelial cells, the abnormality of the vascular endothelial cells can be treated through the glycolysis inhibitor, complications, such as after cancer chemotherapy and hematopoietic stem cell transplantation can be reduced, the treatment risk is reduced, the quality of life is improved, the case-fatality rate is reduced, the medical treatment expenses are reduced, the clinical diagnosis and treatment level of the diseases relevant to the abnormality of the vascular endothelial cells is increased, and prognosis is improved.

Description

technical field [0001] The invention relates to the field of biomedicine, in particular to a glycolysis inhibitor and its application in repairing endothelial cell damage. Background technique [0002] Vascular endothelial cells (ECs) are a single layer of squamous epithelial cells located in the intima of blood vessels, constituting the inner wall of blood vessels. In the cardiovascular system, vascular endothelial cells have many functions such as maintaining vascular integrity, regulating vascular movement, anticoagulant and procoagulant, and interacting with hematopoietic cells. Therefore, as a natural barrier between the vessel wall and blood, vascular endothelial cells play an important regulatory role in maintaining blood circulation and maintaining normal physiological functions of the human body. [0003] Animal studies have shown that the self-renewal and multilineage differentiation capabilities of hematopoietic stem cells are strictly regulated by the bone marro...

Claims

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Application Information

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IPC IPC(8): C12Q1/6883G01N33/573A61K31/444A61K45/00A61P7/00
CPCA61K31/444A61K45/00A61P7/00C12Q1/6883C12Q2600/136C12Q2600/158G01N33/573G01N2333/91215G01N2333/916G01N2500/04G01N2800/52
Inventor 黄晓军孔圆吕中石
Owner PEOPLES HOSPITAL PEKING UNIV
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