Bing Zhang1, Jingjing Zhang2, Yiheshan Ainiwaer2, Bichen He3, Qiang Geng3, Luowen Lin3, Xinling Li2. 1. Department of Anesthesiology, The Affiliated Cancer Hospital of Xinjiang Medical University, Urumqi, China zb1325769256@163.com. 2. Department of Anesthesiology, The Affiliated Cancer Hospital of Xinjiang Medical University, Urumqi, China. 3. Xinjiang Medical University Graduate School, Urumqi, China.
Abstract
OBJECTIVE: To investigate the effect of dexmedetomidine (DEX) on myocardial injury induced by renal ischemia/reperfusion (I/R) and to explore the role of the HMGB1-TLR4-MyD88-NF-κB signaling pathway. METHODS: Adult male Wistar rats were randomly allocated into the control group, renal I/R group, renal I/R group pretreated with a low dose of DEX (L-Dex+I/R), renal I/R group pretreated with a medium dose of DEX (M-Dex+I/R), and renal I/R group pretreated with a high dose of DEX (H-Dex+I/R). Outcome measures included the plasma concentrations of HMGB1, IL-6, IL-10, IL-17, and TnI, the expression levels of HMGB1, TLR4, MyD88, NF-κBp65, and P-NF-κBp65, the pathological change, and the cell apoptosis. RESULTS: Renal I/R led to severe myocardial histological injury and cell apoptosis. DEX reduced the plasma concentration of IL-17 and TnI in a dose-dependent manner in the renal I/R model rats and inhibited the protein expression of TLR4 and NF-κBp65 in a dose-dependent manner in the myocardial tissue. Additionally, mRNA expression of MyD88 was elevated in the I/R group compared with the control group, and DEX significantly reduced mRNA expression of MyD88 in the renal I/R model rats. DEX inhibited myocardial cell apoptosis in the renal I/R model rats. CONCLUSION: DEX could attenuate myocardial injury induced by renal I/R in a dose-dependent manner. The potential mechanisms are associated with inhibition of the HMGB1-TLR4-NF-κB signaling pathway and myocardial cell apoptosis.
OBJECTIVE: To investigate the effect of dexmedetomidine (DEX) on myocardial injury induced by renal ischemia/reperfusion (I/R) and to explore the role of the HMGB1-TLR4-MyD88-NF-κB signaling pathway. METHODS: Adult male Wistar rats were randomly allocated into the control group, renal I/R group, renal I/R group pretreated with a low dose of DEX (L-Dex+I/R), renal I/R group pretreated with a medium dose of DEX (M-Dex+I/R), and renal I/R group pretreated with a high dose of DEX (H-Dex+I/R). Outcome measures included the plasma concentrations of HMGB1, IL-6, IL-10, IL-17, and TnI, the expression levels of HMGB1, TLR4, MyD88, NF-κBp65, and P-NF-κBp65, the pathological change, and the cell apoptosis. RESULTS: Renal I/R led to severe myocardial histological injury and cell apoptosis. DEX reduced the plasma concentration of IL-17 and TnI in a dose-dependent manner in the renal I/R model rats and inhibited the protein expression of TLR4 and NF-κBp65 in a dose-dependent manner in the myocardial tissue. Additionally, mRNA expression of MyD88 was elevated in the I/R group compared with the control group, and DEX significantly reduced mRNA expression of MyD88 in the renal I/R model rats. DEX inhibited myocardial cell apoptosis in the renal I/R model rats. CONCLUSION: DEX could attenuate myocardial injury induced by renal I/R in a dose-dependent manner. The potential mechanisms are associated with inhibition of the HMGB1-TLR4-NF-κB signaling pathway and myocardial cell apoptosis.