Application of Nrf2-based cyclovirobuxinum D in diabetic cardiomyopathy

A technology of diabetic cardiomyopathy and Cyclovir buxicine is applied in the field of medical inventions to achieve the effects of increased cardiac dysfunction, reduced ejection fraction, and improved cardiac function

Inactive Publication Date: 2020-04-10
GUIZHOU MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Previous studies have shown that CVB-D has the pharmacological effects of anti-oxidative stress and stimulating autophagy, and has good curative effect on various cardiovascular diseases such as arrhythmia, angina pectoris and coronary heart disease[11,12]. Whether heart disease is effective has not yet been reported

Method used

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  • Application of Nrf2-based cyclovirobuxinum D in diabetic cardiomyopathy
  • Application of Nrf2-based cyclovirobuxinum D in diabetic cardiomyopathy
  • Application of Nrf2-based cyclovirobuxinum D in diabetic cardiomyopathy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0050] Effects of CVB-D on Cardiac Function and Survival Rate of DCM Rats

[0051] The establishment of DCM rat model: high-fat diet (18% of animal fat, 20% of sucrose, 2% of cholesterol, 0.2% of bile salt, 59.8% of basal feed) fed 2-month-old SD rats for 3 months, and blood was taken from the tail for determination Serum fasting insulin and blood sugar concentration, evaluate insulin resistance by 1 / fasting insulin * fasting blood sugar, intraperitoneally inject 25 mg / kg STZ to insulin resistant rats, inject the same volume of sodium citrate buffer solution in the control group, and measure random blood sugar with a blood glucose meter after 72 hours , ≧ 11.1mM for T2DM model success. After establishing the T2DM model, the experiment was divided into: normal control group, model group, M+CVB-D high-dose group (2mg / kg / d, intragastric administration), M+CVB-D low-dose group (1mg / kg / d , intragastric administration), the positive drug rapamycin group (2mg / kg, once every other da...

Embodiment 2

[0054] Effects of CVB-D on cardiac oxidative stress in DCM rats

[0055] The left ventricle was taken to detect SOD and MDA levels; HE staining was used to observe pathological changes; transmission electron microscopy was used to observe the morphology of cardiac mitochondria; Western blot was used to detect the expression of Nrf2, NQO-1, prdx1; expression;

[0056] Results: HE staining of heart tissue showed inflammatory cell infiltration in the heart of DCM rats (Fig. 2-a), and TEM indicated mitochondrial cristae damage ( figure 2 -b); DNA oxidative damage marker 8-OHdG immunohistochemical staining showed that the positive rate of the model group was significantly higher than that of the normal control group ( figure 2 -c, d); ELISA kit detection found that the peripheral blood SOD level of the model group decreased ( figure 2 -e), MDA level increased ( figure 2 -f), the above results suggest that the heart oxidative stress injury of DCM rats, after the intervention ...

Embodiment 3

[0058] Effects of CVB-D on cardiac autophagy in DCM rats

[0059] The expressions of Nrf2, p62 and LC3 in heart tissue of rats in each group were detected by western blotting and immunofluorescence, and the number of cardiac autophagosomes was observed by transmission electron microscope.

[0060] Results: Transmission electron microscopy showed that the number of autophagic lysosomes in the heart of rats in the model group decreased (Fig. image 3 -B); Immunofluorescence results were similar, and suggested that Nrf2, LC3 and p62 co-localized ( image 3 -C). Values ​​are represented by mean ± SD, each group n=3, by t test, *P<0.05vs. control group; #P<0.05vs. model group.

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Abstract

The invention relates to an application of Nrf2-based cyclovirobuxinum D in diabetic cardiomyopathy. An Nrf2 pharmacological agonist and inhibitor, and Nrf2 shRNA and overexpression plasmids are usedto prove that the cyclovirobuxinum D can improve oxidative stress and activation autophagy through a Nrf2 signal to improve the diabetic cardiomyopathy and provide a research basis for expanding the clinical application scope of the cyclovirobuxinum D.

Description

technical field [0001] The invention relates to the field of medical inventions, in particular to the application of Nrf2-based Cyclovirubuxin D in diabetic cardiomyopathy. Background technique [0002] Currently, at least 425 million adults worldwide suffer from diabetes. Diabetes and its complications have become one of the major public health problems in the 21st century, bringing heavy burdens to families and society [1]. Diabetic cardiomyopathy (diabetic cardiomyopathy, DCM) is a specific cardiomyopathy caused by diabetes, and the incidence rate in diabetic patients is about 10-30%. Since Lundbaek first proposed this unique clinical phenomenon in 1954, DCM is usually described as cardiac structural abnormality and dysfunction, with abnormal systolic and diastolic function in the early stage and heart failure in the late stage. It is the main cause of death in diabetic patients [2]. At present, there is no specific drug for the treatment of DCM. After adopting conventi...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/57A61P3/10A61P9/00
CPCA61K31/57A61P3/10A61P9/00
Inventor 沈祥春蒋朝辉付凌云陶玲
Owner GUIZHOU MEDICAL UNIV
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