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Medicinal uses of nitrosoglutathione reductase

A drug and a technology for diabetic blood vessels, applied in the field of diabetes prevention and treatment, can solve problems such as unclear specific mechanisms, and achieve the effect of inhibiting vascular endothelial dysfunction

Active Publication Date: 2020-09-08
NANJING MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, whether GSNOR plays a regulatory role in diabetic vascular lesions and its specific mechanism is still unclear. At the same time, whether the GSNOR inhibitor N6022 can play a therapeutic role in diabetes-related vascular lesions has not yet been reported.

Method used

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  • Medicinal uses of nitrosoglutathione reductase
  • Medicinal uses of nitrosoglutathione reductase
  • Medicinal uses of nitrosoglutathione reductase

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] Example 1: In a diabetes model, the expression level of GSNOR in endothelial cells is significantly increased.

[0028] In order to study whether diabetes affects the protein level of GSNOR in endothelial cells, we treated human umbilical vein endothelial cells (HUVEC) with high glucose (30mM) for 24h, and Western blot showed that the expression of GSNOR in endothelial cells treated with high glucose was significantly increased ( figure 1 ); In the mouse type 1 diabetes model induced by streptozotocin (STZ), the aortic vascular tissue of the mouse was taken, and Western blot detection found that the expression of GSNOR in the vascular tissue of the diabetic mouse was significantly increased ( figure 2 ), the immunofluorescence of mouse aortic tissue sections also showed that the expression of GSNOR in the vascular endothelium of diabetic mice was significantly increased ( image 3 ).

Embodiment 2

[0029] Example 2: Inhibition of GSNOR can improve diabetic vascular endothelial dysfunction.

[0030] In order to further study whether the increase of GSNOR protein level is involved in the occurrence of diabetic vascular endothelial dysfunction. At the cellular level, we used small interfering RNA (sense: GCUGAUAUCUCUGUUGCUATT, antisense: UAGCAACAGAGAUAUCAGCTT) to knock down GSNOR, and then treated with high glucose (30mM) for 24 hours. The results of endothelial cell tube formation experiments showed that after knocking down GSNOR, the high Sugar-induced disruption of endothelial cell junctions ( Figure 4 ) and an increase in endothelial cell permeability ( Figure 5 ); at the same time, after administration of GSNOR inhibitor N6022 (10nM), it can significantly improve the damage of high glucose-induced junctions between endothelial cells ( Figure 6 ) and an increase in endothelial cell permeability ( Figure 7 ); In the streptozotocin (STZ)-induced type 1 diabetes mou...

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Abstract

The invention relates to medical application of nitrosoglutathione reductase, belongs to the technical field of diabetes prevention and treatment, and particularly relates to the application of regulating nitrosoglutathione reductase GSNOR in prevention and treatment of diabetic vascular endothelial dysfunction. By transfecting small interfering RNA, knocking out a GSNOR gene or injecting an inhibitor N6022, and inhibiting the expression or activity of GSNOR, the vascular endothelial dysfunction caused by diabetes can be effectively inhibited.

Description

technical field [0001] The invention belongs to the technical field of diabetes prevention and treatment, and specifically relates to the application of regulating nitrosoglutathione reductase GSNOR in the prevention and treatment of diabetic vascular endothelial dysfunction. Background technique [0002] Diabetes is a metabolic disease characterized by hyperglycemia. Currently, nearly 400 million people worldwide suffer from diabetes. Diabetes can cause damage to a variety of target organs, leading to a series of complications, such as diabetic retinopathy, diabetic nephropathy, diabetic cardiomyopathy and so on. These diabetic complications seriously endanger the life and health of diabetic patients. At the same time, vascular disease caused by long-term hyperglycemia in diabetes is the main cause of various target organ damage. Vascular lesions are mainly manifested as endothelial cell injury, inflammatory cell recruitment, and smooth muscle cell proliferation and migra...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12Q1/26A61K31/713A61P3/10
Inventor 季勇谢利平赵爽宋天宇孙世秀缪青
Owner NANJING MEDICAL UNIV
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