Application of thrombin aPC in drugs for prevention and treatment of diabetic cardiomyopathy

A technology of diabetic cardiomyopathy and coagulation protease, which is applied in the field of application of coagulation protease aPC in the prevention and treatment of diabetic cardiomyopathy drugs, and can solve problems such as the relationship between YB-1 that has not been reported in research

Active Publication Date: 2018-06-15
TONGJI HOSPITAL ATTACHED TO TONGJI MEDICAL COLLEGE HUAZHONG SCI TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, there is still no research report on the relationship between YB-1 and the occurrence and development of DCM

Method used

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  • Application of thrombin aPC in drugs for prevention and treatment of diabetic cardiomyopathy
  • Application of thrombin aPC in drugs for prevention and treatment of diabetic cardiomyopathy
  • Application of thrombin aPC in drugs for prevention and treatment of diabetic cardiomyopathy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] Therapeutic effect of coagulation protease aPC on cardiac insufficiency in mice with diabetic cardiomyopathy

[0031] Male C57BL6 / J mice (8 weeks old) were randomly divided into 3 groups: control group, diabetes group and aPC treatment group. Using multiple small doses of streptozotocin (STZ, dissolved in citric acid buffer solution of 0.05M pH4.5, 60mg / kg) administration method, the mice in the diabetes group and the aPC treatment group were injected intraperitoneally with the STZ solution for 5 consecutive days. Group intraperitoneally injected citrate buffer ( figure 1 ). 22 weeks after injection of STZ, the left ventricular ejection fraction (left ventricular ejection fraction, LVEF), left ventricular fractional shortening (left ventricular fractional shortening, LVFS), left ventricular diastolic or systolic interventricular septal thickness ( left ventricular internal dimension at diastole and systole, LVIDd and LVIDs), left ventricular posterior wall thickness (...

Embodiment 2

[0035] Coagulation protease aPC inhibits the degradation of YB1 protein in cardiomyocytes

[0036] H9C2 cells were randomly divided into groups: PBS control group, proteasome inhibitor MG132 treatment group, coagulation protease aPC intervention group. According to the above grouping, the protein synthesis inhibitor CHX (10mg / ml) was given for 1 hour, followed by PBS, MG132, and coagulation protease aPC for 0, 1, 3, 6, and 12 hours, and the cell protein was collected and quantified by BCA method. , take 20ug / well Western Blot to detect the expression of YB-1 and internal reference protein GAPDH.

[0037] The results showed that Western Blot results showed that coagulation protease aPC could significantly inhibit the degradation of cardiomyocyte YB1 protein ( Figure 7 ).

[0038] The experimental conclusion confirms that the blood coagulation protease aPC involved in the present invention can stabilize the expression of cardiomyocyte YB1 protein.

Embodiment 3

[0040] Coagulation protease aPC inhibits the ubiquitination level of YB1 protein in cardiomyocytes

[0041] After H9C2 cells were treated with high glucose for 0, 1, 3, 6, 12, and 24 hours, the cell protein was collected, and the ubiquitination level of YB1 protein was detected by co-immunoprecipitation assay.

[0042] H9C2 cells were divided into 3 groups: control group, high glucose treatment group, high glucose plus coagulation protease aPC treatment group. According to the above grouping, the high glucose plus coagulation protease aPC treatment group was given coagulation protease aPC intervention for 1 hour, and the high glucose treatment group and the high glucose plus coagulation protease aPC treatment group were intervened in high glucose for 3 hours respectively, then cell proteins were collected and co-immunoprecipitated The ubiquitination level of YB1 protein in each group was detected experimentally.

[0043] All cell experiments added with high glucose stimulatio...

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Abstract

The invention discloses an application of thrombin aPC in drugs for prevention and treatment of diabetic cardiomyopathy induced by streptozotocin. The thrombin aPC can stabilize the expression of YB1by inhibiting ubiquitination of a cardiac muscle cell YB1 in a hyperglycemic state, so as to alleviate cardiomyocyte hypertrophy and fibrosis. The therapeutic study results indicate that the thrombinaPC has significant curative effects of alleviating cardiomyocyte hypertrophy and fibrosis, improving myocardial contractile functions and increasing ejection fraction.

Description

technical field [0001] The invention belongs to the technical field of new application of medicines, in particular, it relates to the application of coagulation protease aPC in medicines for preventing and treating diabetic cardiomyopathy. Background technique [0002] Diabetic cardiomyopathy (DCM) is a structural and functional disorder of the heart caused by diabetes mellitus, independent of hypertension, coronary atherosclerotic heart disease, valvular heart disease, and other known heart diseases. It usually manifests as progressive left ventricular hypertrophy and diastolic and / or systolic dysfunction, and its pathological features include cardiomyocyte hypertrophy, apoptosis, microvascular lesions, and interstitial fibrosis. In 1972, Rubler first proposed the concept of diabetic cardiomyopathy. Over the past 40 years, domestic and foreign scholars have conducted a large number of basic and clinical research in this field, and confirmed that DCM is the main cause of hig...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/17A61P3/10A61P9/00
CPCA61K38/1709
Inventor 曾和松王洪杰王涛
Owner TONGJI HOSPITAL ATTACHED TO TONGJI MEDICAL COLLEGE HUAZHONG SCI TECH
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