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Medical use of n6022 in the treatment of diabetic peripheral arterial disease

A technology for peripheral arterial disease and diabetes, which is applied in the application field of preparing medicines for treating peripheral arterial disease (PAD) of diabetes, and achieves the effects of improving endothelial cell migration and improving blood flow recovery.

Active Publication Date: 2020-03-31
NANJING MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, whether N6022 can improve diabetic peripheral arterial disease (PAD) and its mechanism have not yet had any relevant research and reports

Method used

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  • Medical use of n6022 in the treatment of diabetic peripheral arterial disease
  • Medical use of n6022 in the treatment of diabetic peripheral arterial disease
  • Medical use of n6022 in the treatment of diabetic peripheral arterial disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0018] Example 1: The effect of N6022 on the improvement of lateral limb ischemia in diabetic lateral limb ischemia model mice

[0019] In order to explore the effect of N6022 on lateral limb ischemia in diabetic lateral limb ischemia model mice, we selected SPF grade 8-week-old male C57BL / 6 mice (purchased from the Medical Experimental Animal Center of Nanjing Medical University) and randomly divided them into five groups : solvent control group, diabetes model solvent control group and three different N6022 concentrations (0.01mg / kg / day, 0.1mg / kg / day, 1mg / kg / day) diabetes model administration groups. Among them, the diabetes model was administered by intraperitoneal injection of streptozotocin (STZ) 60mg / kg / day for 5 consecutive days at the 8th week of the mouse, and blood glucose >16.6 mmol / L was measured at the 10th week. For the limb ischemia model, different concentrations of N6022 (0.01mg / kg / day, 0.1mg / kg / day, 1mg / kg / day) and the control solvent DMSO were injected throu...

Embodiment 2

[0024] Example 2: Improvement effect of N6022 on the reduction of endothelial cell migration and tube-forming ability caused by high glucose

[0025]It is known that in diabetic peripheral arterial disease (PAD), decreased angiogenesis is one of the risk factors for severe ischemia followed by ulceration and amputation. In order to study the effect of GSNOR inhibitor N6022 on endothelial cell function damage caused by high glucose , so we tested the angiogenesis ability at the cell level through the tube formation experiment, seeded HUVEC (2*10^4) into the coagulated Matrigel 24-well plate, and administered different concentrations of N6022 (1nM, 10nM, 100nM), The mannitol group was the isotonic control of high glucose, and the angiogenesis was detected after 24 hours. And we tested the migration ability of endothelial cells by scratch test, transwell test and spheroid capillary sprouting assay. The above experiments all showed that N6022 can significantly reverse the decline ...

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Abstract

The invention relates to medical application of N6022 in treating diabetic peripheral arterial diseases, and relates to the cardiovascular field. At an animal level, in a diabetic mouse side limb ischemia model, by means of tail vein injection of N6022, blood flow recovery can be improved, angiogenesis of skeletal muscles can be improved, and the diabetic peripheral arterial diseases can be alleviated. At a cell level, by giving a GSNOR inhibitor, N6022 can alleviate reduction, caused by high glucose, of the human umbilical vein endothelial cell (HUVEC) migration capacity and vessel formationcapacity. A new application field of N6002 is exploited, and a meaningful reference is provided for treating the diabetic peripheral arterial diseases and improving diabetic vascular lesion conditions.

Description

technical field [0001] The invention belongs to the technical field of diabetic peripheral arterial disease, and in particular relates to the application of N6022, an inhibitor of nitrosoglutathione reductase (GSNOR), especially in the preparation of drugs for treating diabetic peripheral arterial disease (PAD). Background technique [0002] Peripheral arterial disease (PAD) of the lower extremities has a high prevalence, reaching 20% ​​to 40% in people with diabetes. With the increase of age, the risk of PAD in diabetic patients increases by 2 to 4 times, which is the most important risk factor. PAD has high morbidity and mortality rates. The stenosis and occlusion of lower extremity arteries caused by PAD lead to severe limb ischemia (CLI), the slowing of wound healing caused by factors such as angiogenesis reduction and collateral circulation formation obstacles, not only the risk of diabetic foot It is also one of the independent risk factors leading to amputation in dia...

Claims

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Application Information

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IPC IPC(8): A61K31/4178A61P3/10A61P9/14
CPCA61K31/4178A61P3/10A61P9/14
Inventor 季勇谢利平宋天宇赵爽孙世秀
Owner NANJING MEDICAL UNIV
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