Inflammatory and oxidative stress‑associated factors in chronic intermittent hypoxia in Chinese patients, rats, lymphocytes and endotheliocytes.

Abstract

In order to investigate the association between inflammatory and oxidative stress (OS)-associated factors in chronic intermittent hypoxia (CIH), 238 CIH patients and 156 healthy volunteers were included. CIH rat and lymphocytes were used as experimental models. Interleukin (IL)-6, tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), nitric oxide (NO) and nitric oxide synthase (NOS) were analyzed. Patients with CIH were older, with hypertension, increased heart rate (HR) and body mass index (BMI), and there were more males than females. Those with a history of smoking or type 2 diabetes (T2DM) history exhibited an increased risk of CIH. Serum IL-6, TNF-α and CRP in patients with CIH were increased, while NO and NOS were decreased. Hakka patients exhibited increased BMI measurements and NO expression, and decreased systolic arterial pressure, IL-6 and TNF-α compared with non-Hakka patients. Rats with CIH exhibited hypertension and stable weight, less activity and decreased appetite, increased HR and serum IL-6, TNF-α and CRP, and decreased NO and NOS. IL-6, TNF-α, CRP, NO and induced-NOS (iNOS) were increased in the lymphocytes of CIH rats compared with healthy ones. In rat endotheliocytes induced by CIH, IL-6, TNF-α, CRP and iNOS increased, while NO and endothelial-NOS (eNOS) decreased. In the supernatant of co-cultured lymphocytes and endotheliocytes, IL-6, TNF-α and CRP increased, although NO and NOS decreased. In conclusion, age, male gender, BMI, smoking and T2DM history, serum IL-6, TNF-α and CRP were positively correlated with CIH combined with hypertension, while NO and NOS were negatively correlated with CIH. Serum NO was predominantly synthesized and released by eNOS. Hakka patients exhibited decreased inflammation and OS with CIH. Increasing IL-6, TNF-α and CRP, and decreasing NO and NOS are biomarkers of CIH, which could be targets in diagnosis, treatment and prevention of CIH.