CN-122005547-A - Application of vitamin C in preparation of medicine for preventing and treating vascular injury caused by microbial infection

CN122005547ACN 122005547 ACN122005547 ACN 122005547ACN-122005547-A

Abstract

The invention discloses an application of vitamin C, or stereoisomers, geometric isomers, tautomers, nitrogen oxides, hydrates, solvates, metabolites, pharmaceutically acceptable salts or prodrugs thereof in preparing medicaments for preventing and treating vascular injury caused by microbial infection. The invention discloses a molecular mechanism of improving endothelial barrier function by regulating ATP11C expression and inhibiting phosphatidylserine eversion of vitamin C, provides a new action target for treating endothelial injury related to infection, verifies the obvious effects of vitamin C in improving endothelial dysfunction caused by infection, reducing vascular leakage and improving survival rate of infected animals through cell experiments and animal experiments, has good application prospect and clinical conversion value, and definitely provides the application of vitamin C in treating vascular endothelial injury caused by staphylococcus aureus, hantavirus and dengue virus infection for the first time, and expands new medical application of vitamin C.

Inventors

ZENG CHUNYU
WU GENGZE
HAN YU
SHU TINGTING
Jiang yuanyang
LI LIANGPENG

Assignees

中国人民解放军陆军特色医学中心

Dates

Publication Date: 20260512
Application Date: 20260410

Claims (4)

1. The application of vitamin C as a compound shown in a formula I, or stereoisomers, geometric isomers, tautomers, nitrogen oxides, hydrates, solvates, metabolites, pharmaceutically acceptable salts or prodrugs thereof in preparing medicaments for preventing and treating vascular injury caused by microbial infection: I。
2. The use according to claim 1, wherein the vascular injury caused by the microbial infection comprises one or more of a bacterial infection, a fungal infection or a viral infection, and further developed sepsis.
3. The use of claim 2, wherein the vascular endothelial injury comprises one or more of impaired endothelial cell barrier function, increased permeability, or decreased endothelial cell viability.
4. The use according to claim 2, wherein vitamin C inhibits phosphatidylserine eversion and apoptosis by inhibiting ATP11C enzyme, improving vascular injury.

Description

Application of vitamin C in preparation of medicine for preventing and treating vascular injury caused by microbial infection Technical Field The invention belongs to the technical field of biological medicines, and particularly relates to application of vitamin C in preparation of a medicine for preventing and treating vascular injury caused by microbial infection. Background The statements in this section merely provide background information related to the present disclosure and may not necessarily constitute prior art. Infectious diseases remain a significant cause of high morbidity and mortality worldwide. Among them, staphylococcus aureus infection, hantavirus, dengue virus and other virus infection can damage vascular endothelial cells in a direct or indirect way, and cause vascular permeability increase, endothelial barrier function destruction and Multiple Organ Dysfunction Syndrome (MODS) to become an important pathological basis of infection-related pathological injury. Vascular endothelial cells, which are critical cell types for maintaining vascular homeostasis and barrier function, are extremely susceptible to inflammatory reactions, pathogen attack, oxidative stress, etc. during infection. Studies have shown that Staphylococcus aureus infection can cause endothelial cell injury and vascular leakage by releasing virulence factors and inducing inflammatory reactions, while Hantavirus and dengue virus can directly infect vascular endothelial cells, destroy intercellular connection structures, cause serious vascular permeability abnormality, and clinically show bleeding tendency, shock and even multi-organ failure. In the vascular endothelial injury process caused by infection, asymmetric disruption of endothelial cell membrane phospholipids is one of the important molecular events. Phosphatidylserine (phosphatidylserine, PS) is normally located inside cell membranes and everts under infectious, inflammatory and oxidative stress conditions, forming procoagulant and pro-inflammatory endothelial phenotypes. PS eversion occurs in close association with impaired endothelial barrier function, coagulation activation and inflammation amplification, with ATP11C as a key enzyme for maintaining PS eversion, and its expression or dysfunction is considered to be one of the important molecular bases for infection-induced endothelial injury. At present, the treatment means aiming at staphylococcus aureus, hantavirus and dengue virus infection mainly focus on anti-infection, symptomatic support and organ function maintenance, but aiming at vascular endothelial injury caused by infection, effective and specific prevention and treatment medicines are not available. Therefore, the development of drugs capable of directly protecting vascular endothelial function and improving endothelial barrier integrity has important clinical significance for reducing infection-related complications and improving prognosis. Disclosure of Invention The invention aims to solve the technical problems that the vascular endothelial injury caused by infection lacks an effective and specific intervention means in the prior art at least to a certain extent. Therefore, the main purpose of the invention is to provide an application of vitamin C in preparing a medicine for preventing and treating vascular injury caused by staphylococcus aureus, hantavirus and dengue virus infection. The invention aims at realizing the following technical scheme: The inventors found in the study that vascular endothelial cell function was significantly reduced after infection with staphylococcus aureus, hantavirus and dengue virus, and was characterized by a decreased endothelial cell viability, a disrupted endothelial barrier function and a significantly increased vascular permeability. Further studies have shown that in the vascular endothelial injury process caused by the infection, the asymmetry of endothelial cell membrane phospholipids is destroyed, and phosphatidylserine (phosphatidylserine, PS) everts, and the expression of the key regulatory enzyme ATP11C is significantly up-regulated, thereby promoting endothelial cells to exhibit the pathological phenotype of procoagulant, pro-inflammatory and barrier dysfunction. Based on transcriptome analysis and small molecule drug screening of staphylococcus aureus, hantavirus and dengue virus infection, the invention provides vitamin C as an effective drug for preventing and treating vascular endothelial injury caused by staphylococcus aureus, hantavirus and dengue virus infection. Research results show that vitamin C can obviously inhibit up-regulation of ATP11C expression induced by infection, inhibit endothelial cell apoptosis, improve endothelial cell activity and restore endothelial barrier function, thereby reducing vascular endothelial injury caused by infection. Specifically, the invention provides the following technical scheme: In one aspect, there is provided an application of Vitamin C (Vitamin C