Antioxidant effects of dexmedetomidine in traumatic brain injury rats by activating Nrf2-ARE pathway

Abstract

Objective To investigate the neuroprotective effect of dexmedetomidine in traumatic brain injury (TBI) rat model and the relationship with clearance of oxygen free radicals and the erythroid-derived nuclear factor-related factor 2 (Nrf2)-antioxidant/electrophilic response element (ARE) signal pathway. Methods Healthy adult male SD rats weighing 300-350 g were selected to construct a TBI model. Sixty rats were divided into three groups: sham operation group (Sham group), traumatic brain injury group (TBI group) and dexmedetomidine (TBI+ DEX group) group. In Sham group, only brain skulls were removed. In TBI and TBI+ DEX groups, the rats were all prepared with a modified free-fall device to induce traumatic brain injury . Rats in TBI and TBI+ DEX groups received same amount of saline and dexmedetomidine (100 μg/kg) treatment 1 h after the onset of TBI respectively. Neurological function was evaluated by modified neurological deficit scores (mNss), and cerebral edema was evaluated by brain dry-wet weight method. The enzyme activity kit was used to detect the antioxidant enzymes SOD and MDA after 24 hours of injury. Finally, Western blot, RT-qPCR and immunofluorescence methods were used to detect the expression level of Nrf2-ARE signaling pathway and its downstream molecules HO-1, NQO-1expression. Results Compared with TBI group, mNss scores in DEX group were significantly lower (P<0.05). DEX could significantly reduce brain edema (P<0.05); DEX could significantly reduce the levels of antioxidant enzyme SOD and oxidative stress product MDA (P<0.05). Conclusion DEX can activate Nrf2-ARE signaling pathway to induce the expression of target genes such as antioxidant/detoxifying enzymes downstream to inhibit oxidative stress and exert neuroprotection. Key words: Dexmedetomidine; Nrf2-ARE signal pathway; Traumatic brain injury; Oxidative stress