| Objective: Oxidative stress is one of the important mechanisms of secondary brain injury after TBI,and Nrf2 is the key molecule for the body to resist oxidative stress.Resveratrol is a natural plant polyphenol with antioxidant and anti-inflammatory effects.To study the effect of resveratrol on the expression of Nrf2/HO-1 signaling pathway protein in TBI animals and explore its possible mechanism.Methods: Six Guangxi Bama miniature pigs were selected.After anesthesia,they were given tracheotomy and oxygen.Cerebral hernia model induced by acute intracranial hypertension was established by injecting autologous femoral blood(1ml/min)into the right frontal lobe,temporal lobe and parietal lobe with microinjection pump.(1)ICP ≥ 50 mmhg;(2)the respiratory rate is obviously slowed down(R≤6 beats/min)or tidal breathing or respiratory arrest occurs;(3)Heart rate≤50 beats /min,or≥200 beats/min and/or arrhythmia;(4)Unilateral or bilateral pupils dilated to the edge;(5)CT or MRI of the head showed intracranial hematoma formation and midline deviation,and the model was successfully established if it met three or more.Resveratrol was injected intraperitoneally 1 hour after successful modeling.CT scan was used to examine intracranial hematoma and occupying effect,and brain volume was calculated according to CT area method.Serum samples were taken before blood injection,1 hour after blood injection,3hours after medication,6 hours after medication and 12 hours after medication,respectively.The expressions of TNF-α and IL-6 were measured by Elisa,and the expression of MDA was measured by kit method.Western Blot was used to detect the expression of Nrf2 and HO-1 protein in brain tissue.Results:(1)Six Guangxi Bama miniature pigs,of which six were successfully established,and one died unexpectedly.The average age was(9.20 0.58)months,the weight was(23.60±0.93)kg,and the brain volume was(69.42±3.16)ml.The average blood injection was(10.20±0.58)ml.(2)Western Blot showed that the expression levels of Nrf2 and HO-1protein in brain tissue were significantly increased before blood injection,1h after blood injection,3h after drug administration,6h after drug administration and 12 h after drug administration(P<0.05,P<0.05).This result shows that resveratrol can up-regulate the levels of Nrf2 and HO-1 in brain tissue in TBI model.(3)The IL-6 content before blood injection,1 hour after blood injection,3 hours after drug administration,6 hours after drug administration and 12 hours after drug administration were significantly different(P < 0.05).When comparing every two groups,there were differences before and after blood injection for 1 hour,before and after blood injection for 3 hours,and before and after blood injection for 6 hours(P<0.05).This result shows that resveratrol can down-regulate the level of IL-6 in TBI model,while the level of TNF-α has no statistical significance before and after blood injection(P>0.05).(4)The content of MDA was statistically significant before operation,1h after operation,3h after medication,6h after medication and 12 h after medication(P<0.05).When comparing every two groups,there were differences before blood injection and 6 hours after medication,6 hours after medication and 12 hours after medication(P<0.05).Conclusion:(1)Resveratrol upregulates the expression of Nrf2 and HO-1 protein in TBI animal model,and reduces the concentration of IL-6 in serum.Its mechanism may be that resveratrol activates and inhibits the Nrf2/HO-1 signal transduction pathway and inhibits the inflammatory reaction.(2)Resveratrol down-regulates MDA level in TBI animal model,which may improve oxidative stress after TBI. |
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