| Objective:For pediatric anesthesia,the sevoflurane is the most commonly used clinical inhalation anesthetics and some studies have shown that its potential neurotoxic effect could be essential risk factor of postoperative cognitive dysfunction.In recent years,some studies have reported that the striatum was involved in the progress of COPD,and learning and memory.In addition,the increasing expression of ?-catenin activated by Wnt/ ?-catenin signaling pathway was involved in the progress of embryonic development,cell proliferation,survival and apoptosis,increasing the regeneration of nerve cells.Therefore,this study was designed to investigate the effect of sevoflurane on learning and memory in young rats and to explore the possible mechanism of sevoflurane on learning and memory.Methods: Sixty four 7d SD rats(10 g ~15 g)were randomly(he method of random number)divided into the blank control group(C group)and sevoflurane group(S group),32 in each group.The rats in C group were only inhaled with 60% oxygen for 3 hours and the rats in S group were inhaled with the mixture of 3% sevoflueane and 60% oxygen for 3 hours.After 24h(P8),8 rats were randomly selected from each group,the density of striatal neuron and the index of neuronal apoptosis were measured by HE and TUNEL staining,respectively.Then,the 8 rats were randomly selected from each group,theexpression of?-catenin in striatum was measured by Western blotting.After three weeks(P28),8 rats were randomly selected from the C group and S group,cognitive function: the navigation test and spatial probe test was measured by the water maze behavior test.The escape latency,swimming speed and frequency of crossing the original platform were recorded and analyzed.After 24h(P33),the other 8 rats in each group,the density of striatal neuron and the index of neuronal apoptosis were measured by HE and TUNEL staining,respectively,and the expression of?-catenin in striatum was measured by Western blotting.Results:1.Striatal neuronal density: At P8,the neuronal density in S group was lower than C group(94.0±4.79 v.s.79.8±6.57 n/hp,P<0.01).At P33,there was no significant difference in neuronal density between C group and S group(87.4±3.84 v.s.88.8±9.25 n/hp,P>0.05).In C group,striatal neuronal density was no significant difference between P8 and P33(P>0.05).In S group,striatal neuronal density at P33 was higher than P8(P<0.05).2.Striatal neuronal apoptosis: The neuronal apoptosis index in S group was higher than C group at P8(0.396±0.099 v.s 0.09±0.029,P<0.01).At P33,there was no significant difference in striatum neuronal apoptosis between C group and S group(0.088±0.025 v.s 0.1±0.0255,P>0.01).In C group,there was no significant difference in neuronal apoptosis between P8 and P33(P>0.05).However,the neuronal apoptosis index at P33 was lower than P8 in S group(P=0.000).3.The protein expression of Wnt/?-catenin in the striatum: At P8,compared with C group,the protein expression of Wnt/?-catenin of S group significantly decreased(p=0.034).At P33,there was no significant difference between C group and S group(p=0.848).4.Morris water maze test:(1)The swimming speed:There was no signific ant difference between C group and S group in all time points(P>0.05).(2)Escape latency: At 1st day,there was no significant difference in escape latency between C group and S group(P>0.05).However,at 2th and 4th days,compared with C group,the scape latency increased in S group(P<0.05).(3)Frequency of crossing the original platform: Compared with C group,the frequency of crossing the original platform was significantly decreased in S group(P=0.045).5.Correlation Analysis: The protein expression of Wnt/?-catenin was posi tively correlated with the neuronal density(r=0.5451,p=0.000)and it was negatively correlated with neuronal apoptosis(r=-0.7518,p=0.000).Conclusion:1.The inhalaion with 3% sevoflueane for 3h could cause learning and memory after 3 weeks in young rats.2.The inhalation with 3% sevoflurane for 3hcan induce early nerve injury in young rats:decreased density of neurons in striatum,decreased expression of ?-catenin,and increased neuronal apoptosis in striatum..3.The mechanism of learning and memory resulting sevoflurane could inhibit the Wnt/?-catenin signaling pathway,and increase neuronalapoptosis and decrease neuronal density in striatum in young rats. |
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