The Mechanism of Endogenous Nociceptin/Orphanin FQ(N/OFQ) and β1-adrenoceptor Autoantibody in Promoting Ischemic Arrhythmia in Rats (tmoenabaaipiai)

Shanxi Medical University

Status: Not yet enrolling

Conditions: Acute Myocardial Ischemia

Study type: Observational

Funder types: Other

Identifiers

NCT06947551

HY20240410

Details and patient eligibility

About

In the early stage of ischemic arrhythmia, endogenous N/OFQ regulates the expression of β 1-AA, mediates the internalization of β 1-AR by PKC/ERK1/2, and thus affects the occurrence of arrhythmia. Further clarify the regulatory mechanism of N/OFQ on β 1-AR internalization and arrhythmia, providing experimental basis for drug development and target exploration of clinical ischemic arrhythmia; To observe the relationship between endogenous N/OFQ and β 1-AA in serum of patients with coronary heart disease and diabetes.

Full description

This project mainly involves animal experiments and cell experiments. The part of clinical trials involved is the extraction of autoantibodies to β 1-adrenoceptor (β 1-AA) from the serum of patients with coronary heart disease and diabetes. The purified antibodies are intended to be used as agonists to rapidly increase the concentration of β 1-AA in the body of animals and the environment of cells in a short time, observe the impact of the antibodies on animals and cells, and further clarify that β 1-AA affects the internalization of β 1-AR through PKC/ERK1/2 at the early stage of blood arrhythmia, so as to regulate the occurrence of arrhythmia. After reviewing the literature, we found that β 1-AA exists in patients with ischemic arrhythmia, coronary heart disease, dilated cardiomyopathy, heart failure, diabetes, dogs with dilated heart disease and hypertensive rats. These β 1-AA targets the second extracellular ring of β 1-AR. Moreover, it can produce an agonist like response to spontaneously beating rat cardiomyocytes, inducing ventricular arrhythmias by stimulating β 1-AR and its downstream pathways. This experiment plans to select 60 patients and extract 8ml and 4ml of blood from the elbow vein for centrifugation and serum extraction. β 1-AA will be separated and extracted using a chromatography column; 4ml is used to detect endogenous N/OFQ and β 1-AA levels using an ELISA kit.

Enrollment: 60 estimated patients

Sex: All

Ages: 18 to 85 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:1) Inclusion criteria for patients with diabetes: refer to the diagnostic criteria for type 2 diabetes (T2DM) in the Chinese Guidelines for the Prevention and Treatment of Type 2 diabetes (2017) 2) Inclusion criteria for patients with coronary heart disease: patients with clinically diagnosed coronary heart disease according to the 1979 WHO Diagnostic Criteria for Ischemic Heart Disease, and exclusion criteria include heart failure, tumor, immune disease and diabetes. -

Exclusion Criteria:Exclusion criteria for patients with coronary heart disease: including heart failure, tumor, immune disease and diabetes. -

Trial design

60 participants in 1 patient group

Patients with coronary heart disease or diabetes under different course of disease

Description:

Select patients with coronary heart disease and diabetes who meet the standard, take 8ml of blood from the elbow vein, 4ml of blood for centrifugation, take serum, and use chromatography column to separate and extract β 1-AA; 4ml is used to detect endogenous N/OFQ and β 1-AA levels using an ELISA kit.