Effects of dexmedetomidine pretreatment on TNF-α and IL-6, oxidative stress and myocardial apoptosis of rats after myocardial ischemia-reperfusion injury

Objective: This study aimed to investigate the effects of dexmedetomidine pretreatment on the levels of inflammatory cytokines TNF-alpha and IL-6 of rats after myocardial ischemia-reperfusion injury. Methods: 120 SPF SD male rats were randomly divided into control group (Cgroup), model group (Mgroup), pretreatment of dexmedetomidine group (PDgroup), PI3K broad-spectrum inhibitor LY 294002 pretreatment group (LYgroup) and the dexmedetomidine + LY 294002 pretreatment group (D&Lgroup). Before the ischemia-reperfusion, the PD group was treated with intravenous drip of 6 mu g/kg/h dexmedetomidine for 10 minutes, and followed by intravenous drip of 7 mu g/kg/h dexmedetomidine for 15 minutes. The LY group was treated with intravenous injection of 0.3 mg/kg LY 294002. D&L group was treated with intravenous drip of LY 294002, and followed by dexmedetomidine administration at the same dose as before. After successful modelling, the left ventricular diastolic blood pressure, systolic blood pressure and heart rate were detected by electrophysiological signal recorder. Peripheral blood samples were collected from the abdominal aorta to detect related indexes of cardiac function (CK, CK-MB, cTnI). Finally, the rat's heart was cut out. TNF-alpha, IL-6, superoxide dismutase (SOD), malondialdehyde (MDA), Bax, Bcl-2 and phosphorylated protein kinase B (p-AKT) level in rat's myocardial tissue were detected by ELISA. The correlation between p-AKT and left ventricular diastolic blood pressure, systolic blood pressure, heart rate, CK, CK-MB, cTnI, TNF-alpha, IL-6, SOD, MDA, Bax, Bcl-2 was analyzed. Results: Dexmedetomidine pretreatment can effectively improve left ventricular diastolic blood pressure, systolic blood pressure, heart rate, CK, CK-MB, cTnI, TNF-alpha, IL-6, SOD, MDA, Bax, and Bcl-2 levels, and promote p-AKT levels (P < 0.05). LY 294002 holds the opposite effect with dexmedetomidine. It can reduce the protective effect of dexmedetomidine. p-AKT levels are associated with SOD and Bcl-2 levels (P < 0.05). Conclusion: Dexmedetomidine pretreatment can effectively reduce the myocardial cell inflammation and oxidative stress levels of rats after myocardial ischemia-reperfusion, decrease myocardial cell apoptosis, and protect cardiac function. This effect is related to the activation of PI3K/AKT signaling pathway.