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Application of substance for improving activity and/or expression quantity of liver SIRT5 protein in treatment of acute myocardial infarction

A technology for acute myocardial infarction and protein activity, which is applied in the field of biomedicine and can solve problems such as few researches on the effect

Active Publication Date: 2021-06-18
BEIJING TSINGHUA CHANGGUNG HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Studies have also shown that lysine succinylation plays an important regulatory role in diseases with active energy metabolism, such as tumors, diabetes, stroke, liver disease, etc., but there are few studies on the role of lysine succinylation in heart diseases

Method used

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  • Application of substance for improving activity and/or expression quantity of liver SIRT5 protein in treatment of acute myocardial infarction
  • Application of substance for improving activity and/or expression quantity of liver SIRT5 protein in treatment of acute myocardial infarction
  • Application of substance for improving activity and/or expression quantity of liver SIRT5 protein in treatment of acute myocardial infarction

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0045] Embodiment 1, the construction of the acute myocardial infarction model of mouse left anterior descending coronary artery ligation (hereinafter referred to as mouse acute myocardial infarction model)

[0046] 1. Method for constructing mouse model of acute myocardial infarction

[0047]Male mice aged 8-10 weeks were taken and fasted for 12 hours before operation without water. Using 2% pentobarbital sodium intramuscular injection (90mg / kg), postoperative morphine analgesia. Intraoperative monitoring of mouse limb II lead electrocardiogram. After stable anesthesia, the supine position was fixed, the skin of the neck was cut and the muscles were bluntly separated, the trachea was cut and intubated, the small animal ventilator was connected, and the electrocardiogram was continuously monitored. Hair removal on the chest area of ​​the mouse, cut the chest skin obliquely along the left 3-4 intercostal space about 2cm, and bluntly separate the precostal muscles and intercos...

Embodiment 2

[0053] Example 2. Acute myocardial infarction leads to a significant reduction in the succinylation modification of albumin lysine in peripheral plasma

[0054] 1. The inventors of the present invention The inventors analyzed the protein profiles in the plasma of the ctl group (composed of 6 healthy volunteers (ctl)) and the STEMI group (composed of 6 patients with acute ST-segment elevation myocardial infarction (STEMI)).

[0055] The results showed that succinylation (Succ), malonylation (Mal) and glutarylation (Glut) modifications of lysine (K) could be detected in both STEMI and ctl plasma (see Table 1).

[0056] Table 1

[0057]

[0058] The relative contents of protein succinylation, malonylation and glutarylation modification in peripheral plasma of STEMI group, peripheral plasma of ctl group and coronary aspirated plasma of STEMI group were compared. See some results figure 2 (Albumin is albumin, K is lysine, Succ is succinylated modification). The results showe...

Embodiment 3

[0064] Example 3. The myocardial infarction area and myocardial fibrosis area of ​​mice overexpressing SIRT5 protein specifically in the liver were significantly reduced, and cardiac function was improved

[0065] Since albumin only needs to be metabolized in the liver, acute myocardial infarction in Example 2 resulted in a significant reduction in the succinylation modification of multiple lysine sites in the protein in peripheral plasma, which may be due to the expression of SIRT5 protein in the liver under acute hypoxia caused by the increase in volume. For further verification, the C57BL / 6 mouse acute myocardial infarction model or Liver Sirt5 model constructed in Example 1 was taken. + / + Acute myocardial infarction model in mice, statistics of myocardial infarction area, myocardial fibrosis area, and observation of cardiac function.

[0066] 1. Statistical myocardial infarction size

[0067] 1. Take mice (C57BL / 6 mouse acute myocardial infarction model or Liver Sirt5 +...

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Abstract

The invention discloses application of a substance for improving activity and / or expression quantity of liver SIRT5 protein in treatment of acute myocardial infarction. Experiments prove that compared with a C57BL / 6 mouse, the myocardial infarction area and the myocardial fibrosis area of the C57BL / 6 mouse of which a liver specifically overexpresses the SIRT5 protein are remarkably reduced, and the cardiac function is improved to a certain extent. Therefore, the substance for improving the activity and / or expression quantity of the liver SIRT5 protein can reduce the myocardial infarction area, reduce the myocardial fibrosis area and improve the cardiac function, and acute myocardial infarction is further prevented and / or treated. The application of the substance for improving the activity and / or expression quantity of the liver SIRT5 protein in treatment of acute myocardial infarction has an important application value.

Description

technical field [0001] The invention belongs to the field of biomedicine, and in particular relates to the application of substances for improving the activity and / or expression of liver SIRT5 protein in the treatment of acute myocardial infarction. Background technique [0002] Post-translational modification (PTM) is a modified process such as phosphorylation, acetylation, succinylation, etc. discovered in recent years that proteins undergo after translation, which may affect the spatial configuration and signal transduction of proteins. Thereby altering the biological function of the protein. A large number of basic studies have suggested that PTM plays an important regulatory role in the pathogenic process of acute cardiac ischemia and hypoxia. For example, histamine deacetylase HDAC7 may play a role in restenosis after coronary artery stent implantation by affecting the proliferation and migration of smooth muscle cells. Oxidatively modified high-density lipoproteins m...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/06A61P9/10A61P9/00A01K67/027C12Q1/6883G01N33/573
CPCA61P9/10A61P9/00A01K67/027A01K2207/30A01K2227/105A01K2267/0375A61K45/00
Inventor 周博达张萍卫涛涛陈旭东
Owner BEIJING TSINGHUA CHANGGUNG HOSPITAL
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