NCT06947551

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

• Status: Not Yet Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 60 (estimated)
• Sponsor: Second Hospital of Shanxi Medical University · Academic / Other
• Sex: All
• Age: 18 Years – 85 Years
• Healthy volunteers: Accepted

Summary

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.

Detailed 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.

Conditions

• Acute Myocardial Ischemia

Timeline

• Start date: 2025-05-01
• Primary completion: 2026-05-01
• Completion: 2026-06-01
• First posted: 2025-04-27
• Last updated: 2025-04-27