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Application of NOD signaling pathway induced by abnormal palmitic acid metabolism in diagnosis and prevention of myocardial injury

A myocardial injury and signaling pathway technology, applied in cardiovascular system diseases, active ingredients of sulfonylureas, drug combinations, etc., can solve the problem that the treatment of myocardial injury has not been reported in the literature, and achieve the effect of reducing myocardial injury and reducing the degree of damage.

Inactive Publication Date: 2019-04-12
TIANJIN UNIV OF TRADITIONAL CHINESE MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0005] Glibenclamide is currently mainly used to treat type 2 diabetes, and the treatment of myocardial injury has not been reported in the literature

Method used

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  • Application of NOD signaling pathway induced by abnormal palmitic acid metabolism in diagnosis and prevention of myocardial injury
  • Application of NOD signaling pathway induced by abnormal palmitic acid metabolism in diagnosis and prevention of myocardial injury
  • Application of NOD signaling pathway induced by abnormal palmitic acid metabolism in diagnosis and prevention of myocardial injury

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] 1. Animal experiments: 30 clean-grade male Wistar rats, weighing 200±20g, were divided into two groups on average: (1) The blank group was administered with normal saline at a dose of 2ml (n=15, intragastric administration) , d=7); the aconitine group was given a dose of 0.32 mg / kg of aconitine (n=15, administered by intragastric administration, d=7). After 30 minutes of administration on the seventh day, blood was collected from the abdominal aorta of the rats in each group, and the serum was obtained by centrifugation; the heart was removed, and part of it was subjected to pathological examination; the other part was stored in liquid nitrogen for proteomics and metabolomics academic research.

[0027] 2. Proteomics analysis: Weigh an appropriate amount of heart tissue samples into a mortar pre-cooled with liquid nitrogen, add liquid nitrogen to fully grind to powder. Each group of samples was added with 4 times the volume of powdered lysis buffer (8M urea and 1% prot...

Embodiment 2

[0037] 1. Cells: primary cardiomyocytes were isolated from suckling rat hearts. The separated cells were incubated with DMEM medium containing 10% fetal bovine serum (FBS) and 1% double antibody (penicillin-streptomycin mixed solution) at 37 ℃ with 5% CO 2 Continue subculture in a constant temperature incubator.

[0038] 2. MTT detection: MTT kit (America, Sigma) was used to detect cell viability.

[0039] 3. Western blotting analysis: Cell extracts were obtained by using RIPA lysis buffer, and after the extracts were subjected to SDS-PAGE electrophoresis, proteins were transferred to nitrocellulose membranes by electroblotting. The membrane was then blocked and incubated with antibodies (NF-κB (America, CST), RIP2 (America, Sigma), FADD (America, CST), NLRP3 (America, CST), caspase-1 (America, CST), IL-18 (America, CST), IL-1β (America, CST)). The film obtained after developing the color of the membrane was photographed with the LabWorks TM gel imaging and analysis system,...

Embodiment 3

[0044] practical application

[0045] We compared lactate dehydrogenase (LDH) and creatine kinase-isoenzyme MB (CK-MB) in serum of blank group and aconitine group in animal experiments. The results showed that compared with the normal group, the LDH of the administration group , CK-MB (P<0.01) were significantly increased, indicating that myocardial injury had occurred in the rats, and UPLC / Q-TOF-MS assayed palmitic acid in serum, and the results showed that the level of palmitic acid also increased significantly. This suggests that monitoring palmitate levels can diagnose drug-induced cardiotoxicity.

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Abstract

The invention discloses an application of NOD signaling pathway induced by abnormal palmitic acid metabolism in diagnosis and prevention of myocardial injury, when myocardial gets injured, the level of palmitic acid in body becomes abnormal, the NOD-like receptor signaling pathway is activated to induce inflammation, furthering aggravate myocardial injury. The innovative point of the application is as follows, starting from the above mechanism, applying NLRP3-inhibitor glibenclamide to the prevention of myocardial injury caused by abnormal palmitic acid, myocardial injury can be alleviated byinhibiting the inflammatory response of NOD-like receptor signaling pathway. Meanwhile, finding out the level of palmitic acid in body can diagnose myocardial injury or access the risk of being worsefor patients. The discovery provides heart disease caused by drug toxicity and abnormal lipid metabolism or diagnosis and treatment of diseases in connection with lipid metabolism.

Description

technical field [0001] The invention relates to the application of monitoring palmitic acid level in the diagnosis of myocardial injury and the application of NOD-like receptor signaling pathway inhibitors in the diagnosis and prevention of abnormal palmitic acid myocardial injury. Background technique [0002] Aconitine is a highly toxic alkaloid, and it is the main toxic component in traditional Chinese medicines such as Aconitum, Aconitum, and Aconitum. The heart is the main target organ of aconitine. Aconitine can cause arrhythmia and eventually induce cardiomyocyte apoptosis. However, the current research on the mechanism of heart damage caused by aconitine generally focuses on ion channels, while other causes of heart damage caused by aconitine have not yet been fully elucidated. After the body's metabolism is disturbed, abnormal metabolites may cause further damage, which will compound with the direct damage of the drug to the target organ or tissue to form secondary ...

Claims

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Application Information

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IPC IPC(8): A61K31/64A61P9/00
CPCA61K31/64A61P9/00
Inventor 李遇伯范思邈
Owner TIANJIN UNIV OF TRADITIONAL CHINESE MEDICINE
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