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

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.