Role of NRG1/ErbB4 pathway in sevoflurane-induced cognitive dysfunction in rats
Objective To investigate the role of neuregulin 1(NRG1)/ErbB4 pathway in sevoflurane-induced cognitive impairment in rats.Methods Thirty-two SD rats were randomly divided into control group,sevoflurane group,sevoflurane+NRG1-β1(NRG1 analogue,5 µg/kg)group,sevoflurane+NRG1-β1+AG1478(ErbB4 receptor blocker,2.5 μg/rat)group,with 12 rats in each group.The rats were fed until day 14,Morris water maze test was used to measure the cognitive function,hematoxylin-eosin staining(HE)was used to observe the neurons in hippocampus,apoptosis of hippocampal neurons was detected by TUNEL,ELISA was used to determine the expression of inflammatory factors in hippocampus,WB was used to detect the expression of apoptosis related proteins and NRG1/ErbB4 pathway related proteins in hippocampus.Results Compared with control group,the latency of sevoflurane group was significantly increased,and the number of times of crossing platform and the residence time in the target quadrant was significantly decreased,the cognitive function and hippocampus were seriously damaged,the apoptosis rate(30.17％±6.29％vs.3.06％±0.63％)in hippocampus,the level of inflammatory factors and the expression of apoptosis related proteins were significantly increased,the expression of NRG1(0.21±0.04 vs.1.03±0.15)and p-ERBB4/ErbB4(0.19±0.03 vs.0.98±0.10)was significantly decreased(all P＜0.05).Compared with sevoflurane group,the cognitive function and hippocampal tissue damage in sevoflurane+NRG1-β1 group were alleviated,the apoptosis rate of hippocampal neurons(12.61％±2.61％vs.30.17％±6.29％),the expression of apoptosis related proteins and the level of inflammatory factors were significantly decreased,the expression of NRG1(0.79±0.12 vs.0.21±0.04)and p-ErbB4/ErbB4(1.27±0.13 vs.0.19±0.03)was significantly increased(P＜0.05).AG1478 reversed the alleviating effect of NRG1-β1 on sevoflurane induced cognitive dysfunction in rats.Conclusion NRG1/ErbB4 pathway plays an important role in sevoflurane-induced cognitive dysfunction in rats.Activation of NRG1/ErbB4 pathway can improve cognitive dysfunction in rats.
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