Dexmedetomidine pretreatment alleviates ischemia reperfusion injury-induced inflammatory reaction via inhibition of TLR-4/NF-ΚB signaling pathway

Abstract

Purpose: To study the effect of dexmedetomidine on ischemia-reperfusion injury (IRI)–induced inflammatory response, as well as its underlying mechanism of action. \nMethods: Three groups of healthy adult Sprague Dawley (SD) rats (mean weight, 275 ± 10 g): control, IRI and treatment groups were used. With the exception of control group, ligation was performed on left anterior descending coronary arteries for 30 min and blood perfusion was restored within 100 min to establish IRI. Control group rats were without left ligation. Rats in control and IRI groups received normal saline intraperitoneally 30 min prior to surgery, while the treatment group received 100 μg/kg dexmedetomidine via intraperitoneal injection 30 min before operation. Infarct volume was determined using triphenyl tetrazolium chloride (TTC) staining. IL-6) and TNF-α levels of myocardial tissues and serum were determined using enzyme-linked immunosorbent assay (ELISA). Western blotting was used to determine protein expressions of NF-ΚB and TLR-4 in myocardial tissues. \nResults: Pretreatment with dexmedetomidine markedly decreased infarct volume caused by IRI (p < 0.05). Serum and myocardial TNF-α and IL-6 were significantly upregulated in IRI group, relative to control group, but were downregulated by pretreatment with dexmedetomidine (p < 0.05). There was marked upregulation of NF-ΚB and TLR-4 proteins in IRI rats, relative to untreated rats (p < 0.05). Dexmedetomidine also down-regulated the expressions of these proteins (p < 0.05). \nConclusion: Pretreatment with dexmedetomidine alleviates IRI-induced inflammatory reaction via suppression of TLR-4/NF-ΚB signaling pathway. This finding provides a basis for large-scale clinical trials with dexmedetomidine.