Effect of resveratrol on cognitive function after isoflurane anesthesia in obese rats

Abstract

Objective To evaluate the effect of resveratrol on the cognitive function after isoflurane anesthesia in obese rats. Methods Sixty SPF healthy male Sprague-Dawley rats, aged 4 weeks, weighing 70-80 g, were divided into 4 groups (n=15 each) using a random number table: normal diet plus 30% O2 group (group N+ O), high-fat diet plus 30% O2 group (group H+ O), high-fat diet plus 2% isoflurane group (group H+ I), and reveratrol plus high-fat diet plus 2% isoflurane group (group R+ H+ I). Rats were fed a normal diet for 8 weeks in N+ O group, while animals were fed a high-fat diet for 8 weeks in H+ O, H+ I, and R+ H+ I groups.Starting from 9th week, reveratrol 40 mg·kg-1·d-1 was given into the stomach through a gastric tube for 7 consecutive days in group R+ H+ I, while the equal volume of 1% carboxymethyl cellulose sodium was given instead of reveratrol in the other groups.After the end of drug intervention, animals were exposed to the mixture of 70% nitrogen and 30% oxygen for 4 h in N+ O and H+ O groups or to 2% isoflurane for 4 h in H+ I and R+ H+ I groups.Ten rats were randomly selected on 2nd day after inhaling isoflurane, and Morris water maze test was performed to assess the cognitive function.Five rats were randomly sacrificed on 3rd day after inhaling isoflurane, brains were removed, and hippocampi were isolated for determination of the expression of brain-derived neurotrophic factor (BDNF), tyrosine kinase B receptor (TrkB) and phosphorylated TrkB (p-TrkB) in hippocampal tissues by Western blot.The p-TrkB/TrkB ratio was calculated. Results Compared with group N+ O, the escape latency was significantly prolonged on 3rd and 4th days, the exploration time spent on the original target quadrant was shortened, the expression of BDNF and p-TrkB in hippocampal tissues was down-regulated, and the p-TrkB/TrkB ratio was decreased in group H+ O (P<0.05). Compared with group H+ O, the escape latency was significantly prolonged on 2nd-5th days, the exploration time spent on the original target quadrant was shortened, the expression of BDNF and p-TrkB in hippocampal tissues was down-regulated, and the p-TrkB/TrkB ratio was decreased in group H+ I (P<0.05). Compared with group H+ I, the escape latency was significantly shortened on 2nd-5th days, the exploration time spent on the original target quadrant was prolonged, the expression of BDNF and p-TrkB in hippocampal tissues was up-regulated, and the p-TrkB/TrkB ratio was increased in group R+ H+ I (P<0.05). Conclusion Resveratrol can mitigates the cognitive dysfunction after isoflurane anesthesia in obese rats, and the mechanism may be related to promoting the activation of BDNF/TrKB signaling pathway. Key words: Phenols; Obesity; Isoflurane; Cognition disorders