PMID- 32329867 OWN - NLM STAT- MEDLINE DCOM- 20210329 LR - 20210329 IS - 2284-0729 (Electronic) IS - 1128-3602 (Linking) VI - 24 IP - 7 DP - 2020 Apr TI - Remifentanil improves myocardial ischemia-reperfusion injury in rats through inhibiting IL-18 signaling pathway. PG - 3915-3922 LID - 20858 [pii] LID - 10.26355/eurrev_202004_20858 [doi] AB - OBJECTIVE: To explore the protective effect of remifentanil against myocardial ischemia-reperfusion injury (MIRI) in rats and its mechanism. MATERIALS AND METHODS: The rat models of IRI were established and randomly divided into 1) sham-operation group (S group), 2) IRI rat model group (M group), 3) low-dose remifentanil group (R-L group), 4) moderate-dose remifentanil group (R-M group), and 5) high-dose remifentanil group (R-H group). The rats in R-L group, R-M group, and R-H group were administrated with remifentanil at 0.4 mug/kg/min, 2 mug/kg/min, and 10 mug/kg/min, respectively. The activity of creatine kinase-MB (CK-MB), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) in myocardial cells was detected using the automatic biochemical analyzer, and the apoptosis rate of myocardial cells was detected via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Moreover, the messenger ribonucleic acid (mRNA) and protein levels of related cytokines in myocardial cells were determined through quantitative Polymerase Chain Reaction (qPCR) and Western blotting, and the content of interleukin-1beta (IL-1Symbol ) and IL-18 in peripheral blood was detected via enzyme-linked immunosorbent assay (ELISA). RESULTS: Remifentanil at different concentrations could protect myocardium from IRI, and remifentanil at 2 mug/kg/min and 10 mug/kg/min could significantly down-regulate the myocardial enzyme indexes in IRI myocardial cells (p<0.01). Besides, remifentanil reduced the mRNA expressions of IL-18, INF-gamma, TNF-beta, and IL-1beta (p<0.01), significantly decreased the protein expression of IL-18, and raised the protein expression of IL-18BP, thereby improving myocardial pathological damage. CONCLUSIONS: The protective mechanism of remifentanil on the myocardium of MIRI rats may be related to the inhibition on the IL-18 signaling pathway. FAU - Ni, X-Q AU - Ni XQ AD - Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China. 383836979@qq.com. FAU - Hu, Z-Y AU - Hu ZY LA - eng PT - Journal Article PL - Italy TA - Eur Rev Med Pharmacol Sci JT - European review for medical and pharmacological sciences JID - 9717360 RN - 0 (Interleukin-18) RN - P10582JYYK (Remifentanil) SB - IM MH - Administration, Oral MH - Animals MH - Dose-Response Relationship, Drug MH - Interleukin-18/*antagonists & inhibitors/metabolism MH - Male MH - Myocardial Reperfusion Injury/*drug therapy/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Remifentanil/administration & dosage/*pharmacology MH - Signal Transduction/*drug effects EDAT- 2020/04/25 06:00 MHDA- 2021/03/30 06:00 CRDT- 2020/04/25 06:00 PHST- 2020/04/25 06:00 [entrez] PHST- 2020/04/25 06:00 [pubmed] PHST- 2021/03/30 06:00 [medline] AID - 20858 [pii] AID - 10.26355/eurrev_202004_20858 [doi] PST - ppublish SO - Eur Rev Med Pharmacol Sci. 2020 Apr;24(7):3915-3922. doi: 10.26355/eurrev_202004_20858.