Sevoflurane Alleviates Myocardial Ischemia Reperfusion Injury by Inhibiting P2X7-NLRP3 Mediated Pyroptosis
Autor: | Yang Lan, Yanqiong Zhou, Lesi Chen, Ganggang Shi, Xiaoxia Zheng, Wenfeng Cai, Huimin Shen, Danmei Huang, Ruiming Du, Haiyang Li, Daifei Shen, Jiaxuan Wu, Bin Wang |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
myocardial ischemia reperfusion
hypoxia and reoxygenation QH301-705.5 sevoflurane Pharmacology Biochemistry Genetics and Molecular Biology (miscellaneous) Biochemistry Sevoflurane chemistry.chemical_compound NLRP3 Lactate dehydrogenase medicine Molecular Biosciences Biology (General) Molecular Biology Cellular localization Original Research biology Chemistry pyroptosis Pyroptosis Hypoxia (medical) Malondialdehyde medicine.disease biology.protein Creatine kinase medicine.symptom Reperfusion injury P2X7 medicine.drug |
Zdroj: | Frontiers in Molecular Biosciences, Vol 8 (2021) Frontiers in Molecular Biosciences |
Popis: | Myocardial ischemia is common in aging population. This study investigates the protective effect of Sevoflurane on myocardial ischemia reperfusion injury (MIRI) and its underlying mechanism. A total of 87 patients with a history of myocardial ischemia who underwent abdominal surgery with Sevoflurane general anesthesia were recruited in the study. The clinical data, blood pressure, heart rate, pressure-rate quotient (PRQ) and rate-pressure product (RPP) were recorded. Serum samples were collected and heart-type fatty acid binding protein (H-FABP), ischemia modified albumin (IMA), interleukin-1β (IL-1β), and interleukin-18 (IL-18) were measured to observe whether Sevoflurane anesthesia had protective effect on myocardium. In addition, MIRI rats and hypoxia/reoxygenation (H/R) injury cell model was established using neonatal rat ventricular myocytes (NRVM). Rats or NRVM were pretreated with sevoflurane for 45min before hypoxia. The mRNA expression of purinergic receptor-7 (P2X7) and NLR family pyrin domain containing 3(NLRP3) were examined. The protein expression of P2X7, NLRP3, apoptosis-associated speck-like protein (ASC), cysteine aspartic acid specific protease-1(Caspase-1), Gasdermin-D (GSDMD), Bcl-2 Associated X Protein (Bax), B-cell lymphoma-2 (Bcl-2) in myocardial tissue and cells were evaluated. The serum contents of IL-1β, IL-18, Malondialdehyde (MDA), Superoxide dismutase (SOD), Lactate dehydrogenase (LDH), Creatine kinase (CK), and Creatine kinase isoenzymes (CK-MB) were measured. The cellular localization and fluorescence intensity of NLRP3 and ASC in cells were detected. It was found that the secretion of IL-1β and IL-18 decreased in the patients. After I45 min/R3h in SD rats and H3h/R1h in NRVM, the protein expressions of P2X7, NLRP3, ASC, Caspase-1 and GSDMD were increased, the release of IL-1β, IL-18, CK, CK-MB, LDH and MDA were increased, and SOD activity was decreased. Sevoflurane treatment inhibited the high expression of P2X7, NLRP3, ASC, Caspase-1 and GSDMD, inhibited the release of LDH, CK,CK-MB and MDA in cells, and improved the activity of SOD, indicating that Sevoflurane alleviated the damage of MIRI of rats and H/R of NRVM, and had myocardial protective effect. Taken together, our study suggests that Sevoflurane inhibited the expression of IL-1β, IL-18 and GSDMD by inhibiting the P2X7-NLRP3 signaling pathway. It reduced the H/R injury of cardiomyocytes and protected the cardiac function by regulating inflammatory reaction and pyroptosis. |
Databáze: | OpenAIRE |
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