CN-122005810-A - Application of peroxide reductase 1 as target in preparation of IS therapeutic drugs

Abstract

The invention relates to application of peroxide reductase 1 as a target spot in preparation of IS therapeutic drugs, belonging to the technical field of biological medicines. The invention further screens immune response proteins which are strongly related to the onset risk of ischemic cerebral apoplexy (IS) in plasma, cerebrospinal fluid and brain tissue samples by the steps of high-sensitivity blood immune proteome map construction, large-scale independent queue longitudinal association verification, cross-ethnicity, multi-tissue causality association verification, targeting experiment verification, mechanism exploration, target patency evaluation and treatment potential confirmation and the like, and selects immune response proteins which have obvious differences in patients and controls, and finally discovers the target peroxide reductase 1 (PRDX 1) of the ischemic cerebral apoplexy. The drug, such as PRDX1 agonist or PRDX1 over-expression, IS designed to the drug target, which can effectively improve IS disease progression.

Inventors

• HAN LIYUAN
• ZHAO TIAN
• Pu Liyuan
• HOU ZIYI

Assignees

• 国科宁波生命与健康产业研究院

Dates

Publication Date

20260512

Application Date

20260414

Claims (10)

1. 1. Application of a preparation for up-regulating the expression level of a peroxide reductase 1 coding gene PRDX1 in preparing medicaments for treating or preventing cerebral apoplexy.
2. 2. The use according to claim 1, wherein the agent that up-regulates the expression level of the gene PRDX1 encoding a peroxidase 1 comprises a peroxiredoxin 1 agonist and/or an agent comprising a nucleic acid sequence encoding peroxiredoxin 1.
3. 3. The use according to claim 2, wherein the peroxide reductase 1 agonist comprises one or more of benzothiazine, menaquinone sodium bisulfite.
4. 4. The use according to claim 2, wherein the preparation comprising the nucleic acid sequence encoding the peroxidase 1 comprises a delivery vehicle comprising the nucleic acid sequence encoding the peroxidase 1.
5. 5. The use according to claim 4, wherein the delivery vehicle is a pharmaceutically acceptable vehicle.
6. 6. The use according to claim 1, wherein the Gene ID of the Gene PRDX1 encoding the peroxidase 1 is 5052.
7. 7. The use according to claim 1, wherein the stroke is ischemic stroke.
8. 8. A pharmaceutical composition for treating or preventing ischemic stroke, comprising an agent that up-regulates the level of expression of peroxidase 1.
9. 9. A medicament for treating or preventing ischemic cerebral apoplexy, which is characterized in that the medicament is one or more of benzothiazine, menaquinone sodium bisulfite and a delivery carrier containing a nucleic acid sequence encoding a gene PRDX1 encoding a peroxidase 1.
10. 10. A method of screening for an ischemic stroke therapeutic target, comprising the steps of: s1, screening differential protein in ischemic cerebral apoplexy patients and healthy controls by adopting Olink proteomics method, wherein the differential protein is immune response protein; s2, combining a whole genome association research database, verifying the relation between the level of the immune response differential protein screened in the S1 in blood plasma, cerebrospinal fluid and brain tissue and the incidence risk of ischemic cerebral apoplexy, and obtaining the biomarker of the ischemic cerebral apoplexy according to a verification result.

Description

Application of peroxide reductase 1 as target in preparation of IS therapeutic drugs Technical Field The invention relates to the technical field of biological medicine, in particular to application of peroxide reductase 1 serving as a target point in preparation of IS therapeutic drugs. Background Currently, increased aging of the human mouth and increased vascular risk factors continue to lead to stroke, particularly Ischemic Stroke (IS), which has become a significant public health challenge. IS a leading proportion of all new stroke cases, one of the leading causes of mortality and disability worldwide. Notably, IS particularly burdened with disease in a number of areas including eastern europe and eastern asia, and its age of onset presents a significant trend toward younger age, further exacerbating medical and social burden. Currently, the primary means of treating IS include intravenous thrombolysis and mechanical thrombolysis. The venous thrombolysis is achieved by intravenous infusion of thrombolytic drugs such as alteplase, tenecteplase and the like to dissolve thrombus blocking blood vessels, mechanical thrombolysis belongs to intravascular interventional therapy, microcatheters are placed through femoral artery puncture and reach intracranial occlusion blood vessel positions under image guidance, and thrombus is directly removed or sucked. However, intravenous thrombolysis has strict time window limitation, and is usually carried out within 4.5 hours after the occurrence of the disease, beyond which the curative effect is reduced and the bleeding risk is obviously increased, and mechanical thrombolysis can be prolonged to 24 hours, but is only suitable for patients with anterior circulation large vessel occlusion, and the treatment effect is closely related to the recanalization time, and most patients still miss intervention opportunities due to the delay of treatment. In addition, both recanalization treatments rely on high-precision imaging equipment and special interventional instruments, and the medical cost is high. In addition to recanalization, IS often supplemented with conventional medications such as aspirin and clopidogrel to prevent platelet aggregation, or statin drugs such as atorvastatin, rosuvastatin, etc. are used to stabilize plaque, inhibit inflammation, and improve vascular endothelial function. However, such drugs belong to the basic treatment, have limited protection and repair effects on neurovascular units after ischemia, and are difficult to realize individual precise intervention. In summary, in the field of restoration and treatment of damaged neurological function in IS patients, there IS currently no clinically effective drug or therapy available, and improvement of prognosis of patients faces a great challenge. Thus, aiming at the clinical practice of IS, there IS currently a need to explore new therapeutic targets and intervention strategies to promote repair, improving long-term prognosis of patients. Disclosure of Invention Therefore, the invention aims to solve the technical problem that the prior art lacks effective drugs for ischemic cerebral apoplexy, discovers specific therapeutic targets of ischemic cerebral apoplexy, and provides a series of novel IS therapeutic drugs based on the therapeutic targets. The first object of the present invention is to provide the use of a preparation for up-regulating the expression level of a gene encoding peroxide reductase 1 (PRDX 1) in the preparation of a medicament for treating or preventing cerebral apoplexy. Further, the agents that up-regulate the expression level of peroxidase 1 include, but are not limited to, a peroxidase 1 agonist and/or agents containing a nucleic acid sequence encoding peroxidase 1. Further, the peroxide reductase 1 agonist includes benzothiazine, menaquinone sodium bisulfite, isoflavone, and the like. Further, the formulation comprising a nucleic acid sequence encoding a peroxidase 1 comprises a delivery vector comprising a nucleic acid sequence encoding a peroxidase 1. Further, the delivery vehicle is a pharmaceutically acceptable vehicle, including but not limited to Lipid Nanoparticles (LNP). Further, the Gene ID of the Gene encoding the peroxidase 1 was 5052. Of course, if it is to be used in other species, the PRDX1 encoding gene of the corresponding source may be replaced. Further, the cerebral apoplexy is ischemic cerebral apoplexy. A second object of the present invention is to provide a pharmaceutical composition for treating or preventing ischemic stroke, which contains a preparation for up-regulating the expression level of the peroxidase 1. It is a third object of the present invention to provide a therapeutic or prophylactic agent for ischemic stroke, which is an agent for up-regulating the expression level of peroxidase 1. Further, the drug for up-regulating the expression level of the peroxide reductase 1 is selected from one or more of benzothiazine, menaquinone sodium bisulf