Perioperative changes of serum orphanin in diabetic patients and its relationship with sympathetic nervous system

Diabetes is the disease with the highest incidence in the world except coronary heart disease and hypertension, which poses a serious threat to human health. According to 2015 data from the International Diabetes Federation, the prevalence of diabetes in United Kingdom will reach 7.4% by 2035, with the number of patients reaching 3.6 million (Guariguata et al., 2014). Diabetes is an independent risk factor for the occurrence of cardiovascular diseases, there are often different degrees of myocardial damage, which may be related to the increase in sympathetic nerve activity caused by hyperglycemia and the imbalance of myocardial oxygen supply and oxygen consumption (Balcioglu and Muderrisoglu, 2015; Hussein et al., 2020). However, perioperative stress will further aggravate the imbalance of myocardial oxygen supply and blood supply, leading to myocardial injury, especially for patients with coronary heart disease or patients with limited cardiac function reserves (Landesberg and Jaffe, 2015). Studies have shown that 8–22% of patients will undergo myocardial injury after elective surgery, and the incidence of perioperative myocardial injury is higher in diabetic patients (Ladha et al., 2018). The incidence of perioperative cardiovascular disease and mortality of diabetic patients has increased by 2–3 times compared with non-diabetic patients (Didangelos and Veves, 2020).

The basic research found that the serum Nociceptin/orphanin FQ (N/OFQ) level of diabetes neuropathy rats increased (Liu et al., 2012). N/OFQ fragment can inhibit the degradation of insulin through insulin degrading enzyme (Zingale et al., 2019), and can significantly inhibit the release of insulin from rat pancreatic tissue fragments (Adeghate et al., 2018). This indicates that N/OFQ is involved in the pathological process of diabetes. N/OFQ is an endogenous ligand for NOP receptors and a new endogenous opioid peptide, widely exists in the central and peripheral nervous system and peripheral organs, has the role of active peptides and neurotransmitters. It has been shown to be related to pain, mood disorders and other aspects, participates in the regulation of sports and urinary systems and pain, and plays an important role in the human body (Park et al., 2019; Baiula et al., 2015; Filaferro et al., 2014; Mika et al., 2011). Studies have shown that N/OFQ can inhibit calcium ion channels by activating NOP and activate inward rectifying potassium ion channels to reduce the release of various neurotransmitters such as norepinephrine and produce a certain protective effect on myocardium (Narendran et al., 2019). In our previous laboratory studies, we found that activation of N/OFQ receptor in acute myocardial ischemia induces upregulation of p-RKIP, externalization of β1-adrenergic receptor and downregulation of p-Cx43 in the cardiomyocytes, which promotes ventricular arrhythmia (Han et al., 2013; Han et al., 2022).

Cardiac troponin I (cTnI) is a marker of myocardial injury and necrosis which begins to increase in 3–4 h, reaches the peak in 18–24 h, and appears in the blood circulation for a long time after small myocardial damage be released from myocardial cells with high specificity and sensitivity, and almost exclusively expressed in the myocardium (Fathil et al., 2015).We have always used cTnI as a marker of myocardial injury, but N/OFQ in basic research can appear after 15 min of myocardial injury, the rise time is faster than cTnI (Han et al., 2022). Therefore, studying the N/OFQ content in diabetic patients is of great significance to find new markers of myocardial injury, and exploring its relationship with the sympathetic nervous system can also seek more theoretical basis for improving anesthesia strategies and ensuring patients' anesthesia safety.

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