Effects of isoliquiritigenin on cognitive impairment after sevoflurane-induced fractures in aged rats
Objective To observe the improvement effect of isoliquiritigenin on sevoflurane-induced postoperative cognitive impairment in aged rats and its effect on extracellular signal-regulated kinase 1/2(ERK1/2)/cyclic adenosine monophosphate response unit binding protein(CREB)/brain-derived neurotrophic factor(BDNF)pathway.Methods Forty fractured rats were randomly divided into control group,model group,isoliquiritigenin group and combination group,10 in each group.Rats in the combination group were given isoliquiritigenin(15 mg·kg-1)by gavage,and PD98059(1 mg·kg-1)was injected intraperitoneally.The isoliquiritigenin group was given isoliquiritigenin(15 mg·kg-1)by gavage,and the same volume of dimethyl sulfoxide(DMSO)was injected intraperitoneally.The control group and the model group were given the same amount of DMSO by intragastric administration and intraperitoneal injection,respectively.Once a day,the intervention lasted for 5 days.The cognitive function of rats was detected by water maze test.The expression levels of serum inflammatory factor,such as tumor necrosis factor α(TNF-α)and interleukin 1β(IL-1β)were detected.The apoptosis of hippocampal neurons was observed by Tunel staining.The expression of ERK1/2,p-ERK1/2,CREB,p-CREB and BDNF in hippocampus was detected by Western blot.Results Compared with the model group[(36.26±3.95)s,(23.91±2.91)s,(5.17±0.68)times,(494.42±45.62)ng·mL-1,(600.98±60.01)ng·mL-1,(34.26%±3.96%),(0.23±0.03),(0.14±0.02),(0.16±0.02)],the escape latency of the rats in the isoliquiritigenin group was shortened,the residence time in the third quadrant was prolonged,the number of crossing the original platform was increased,the levels of serum TNF-α,IL-1β,and the apoptosis rate of hippocampal neurons were decreased,and the p-ERK1/2/ERK1/2,p-CREB/CREB and BDNF protein were increased[(14.87±1.43)s,(45.08±4.54)s,(12.31±1.77)times,(253.41±27.61)ng·mL-1,(229.04±23.55)ng·mL-1,(8.53%±1.06%),(0.66±0.11),(0.51±0.05),(0.60±0.07)],P<0.05.Compared with the isoliquiritigenin group,the escape latency of the rats in the combined group was prolonged,the residence time in the third quadrant was shortened,the number of crossing the original platform was reduced,the levels of serum TNF-α,IL-1β,the apoptosis rate of hippocampal neurons were increased,and the p-ERK1/2/ERK1/2,p-CREB/CREB and BDNF protein were decreased[(21.06±2.72)s,(37.17±3.10)s,(7.72±0.96)times,(346.91±44.67)ng·mL-1,(391.38±34.75)ng·mL-1,(16.11%±1.84%),(0.42±0.05),(0.29±0.03),(0.24±0.03)],P<0.05.Conclusion Isoliquiritigenin can improve postoperative cognitive dysfunction,inhibit inflammatory response,and protect neurons in hippocampus,and the activation of ERK1/2/CREB/BDNF signaling pathway may be one of its mechanisms.