Li-Hui Yue1, Li-Na Wang2, Xi-Chun Zhu3, Yan-Hui Peng4. 1. School of Graduate, Hebei Medical University, Shijiazhuang, Hebei Province 050000, China; Department of Anesthesiology and Pain Medicine, Hebei General Hospital, Shijiazhuang, Hebei Province 050000, China. 2. Cardiology Center, Hebei General Hospital, Shijiazhuang, Hebei Province 050000, China. 3. Department of Anesthesiology and Pain Medicine, Hebei General Hospital, Shijiazhuang, Hebei Province 050000, China. 4. School of Graduate, Hebei Medical University, Shijiazhuang, Hebei Province 050000, China; Department of Surgery, Hebei General Hospital, Shijiazhuang, Hebei Province 050000, China. Electronic address: pengyanhuipyhp@126.com.
Abstract
BACKGROUND: This study investigates the effect of dexmedetomidine (DEX), a highly selective agonist of alpha 2-adrenergic receptors (α2-ARs), on the regulation of hepatic macrophage activation in liver regeneration. METHODS: A two-thirds partial hepatectomy (PHx) mouse model was performed. DEX (25 μg/kg) or a vehicle control (saline) was injected i.p. at 30 min before and every 12 h after PHx. The expression of α2B-ARs in the liver was detected using immunofluorescence staining. The effects of DEX on liver regeneration were assessed by Ki67 staining. The gene expression of inflammatory cytokines in isolated hepatic macrophages was quantified 36 h after the PHx. RESULTS: α2B-ARs colocalized with hepatic macrophages after the PHx. The number of Ki67-positive hepatocytes in the mice treated with DEX was markedly increased (p < 0.05). The increases in Ki67-positive hepatocytes after treatment with DEX were inhibited in the macrophage-depleted mice. DEX treatment inhibited the expression of major pro-inflammatory cytokines interleukin (IL)-1β, IL-6, and tumor necrosis factor and elevated the expression of anti-inflammatory cytokines IL-4, IL-10, and transforming growth factor-β1 in hepatic macrophages 36 h after the PHx (p < 0.05). CONCLUSIONS: The α2B-AR subtype is expressed in hepatic macrophages after a PHx. DEX modulates hepatic macrophage activation toward an anti-inflammatory phenotype via α2B-AR, which promotes the process of liver regeneration.
BACKGROUND: This study investigates the effect of dexmedetomidine (DEX), a highly selective agonist of alpha 2-adrenergic receptors (α2-ARs), on the regulation of hepatic macrophage activation in liver regeneration. METHODS: A two-thirds partial hepatectomy (PHx) mouse model was performed. DEX (25 μg/kg) or a vehicle control (saline) was injected i.p. at 30 min before and every 12 h after PHx. The expression of α2B-ARs in the liver was detected using immunofluorescence staining. The effects of DEX on liver regeneration were assessed by Ki67 staining. The gene expression of inflammatory cytokines in isolated hepatic macrophages was quantified 36 h after the PHx. RESULTS: α2B-ARs colocalized with hepatic macrophages after the PHx. The number of Ki67-positive hepatocytes in the mice treated with DEX was markedly increased (p < 0.05). The increases in Ki67-positive hepatocytes after treatment with DEX were inhibited in the macrophage-depleted mice. DEX treatment inhibited the expression of major pro-inflammatory cytokines interleukin (IL)-1β, IL-6, and tumor necrosis factor and elevated the expression of anti-inflammatory cytokines IL-4, IL-10, and transforming growth factor-β1 in hepatic macrophages 36 h after the PHx (p < 0.05). CONCLUSIONS: The α2B-AR subtype is expressed in hepatic macrophages after a PHx. DEX modulates hepatic macrophage activation toward an anti-inflammatory phenotype via α2B-AR, which promotes the process of liver regeneration.