| Objective: To investigate the effects and mechanisms of propofol on cognitive function in young obesity rat.Methods: Four weeks-old male SD rats were randomly divided into two groups: normal diet group and high-fat diet group.The two groups were fed with a normal diet(ND)and a high-fat diet(HFD)for 4 weeks,respectively.Animals in high-fat diet group that were greater than chow control group mean body weight +1.4*Standard Deviation were designated as obesity rats,according to the method that others have previously used.Then,SD rats in each dietary group were divided into two subgroups : normal lipid emulsion solvent group(NL),normal propofol group(NP),obesity lipid emulsion solvent group(OL)and obesity propofol group(OP)(n=20),which were intraperiotoneally administered propofol(100mg/kg)or lipid emulsion solvent(10ml/kg)for 7 days.And then their behavioral performance in a Morris water maze was monitored to determine the cognition of spatial learning and memory.And the plasma S100? protein content of each group was detected by ELISA.The mRNA expression levels of Notch1?Jagged1?HO-1?SOD1 in the rat hippocampus were determined by qPCR.The protein expression levels of Notch1?Jagged1?HO-1?SOD1 in the rat hippocampus were determined by Western blot.And the changes of hippocampal neurons was observed by HE staining in the hippocampus of rat.Results:(1)There was no significant difference in the initial body weight between the normal diet group and the high-fat diet group.After three weeks of feeding,the body weight of the high-fat diet group was significantly higher than that of the normal diet group(P<0.05).After four weeks of feeding,the body weight of the high-fat diet group was significantly higher than that of the normal diet group(P<0.01),40 rats meet the obesity standard,the success rate of obesity modeling is 40%.The feed consumption results showed that the rats in the high-fat diet group was significantly lower than that of the normal diet group(P<0.01).(2)Rats in each group showed a shortening trend during escape latency on days 1-4 and stabilized on days 4 and 5.Compared with that of the OL group,the escape latency of the OP group was longer on days 1-5(P<0.05).Compared with that of the NP group,the escape latency of the NL group was shortened on days 1-2(P<0.05).Compared with those of the NP and OL groups,the OP group showed significantly reduced third quadrant residence time and platform-crossing times(P<0.05).(3)Result of ELISA showed: Compared with the OL group,the S100? protein content in the OP group was significantly increased(P<0.05),and there was no significant difference among NP group,NL group and OL group of the S100? protein content.(4)Results of mRNA showed: Compared with the OL group,the expression of Notch1 and Jagged1 mRNA in the OP group decreased(P<0.05),and there was no significant difference among NP group,NL group and OL group of the mRNA expression.Compared with the OL group,the expression of HO-1 and SOD1 mRNA in the OP group decreased(P<0.05),and there was no significant difference among NP group,NL group and OL group of the mRNA expression.(5)Results of Western blot showed: Compared with the OL group,the expression of Notch1 and Jagged1 protein in the OP group decreased(P<0.05),and there was no significant difference among NP group,NL group and OL group of the protein expression.Compared with the OL group,the expression of HO-1 and SOD1 proteins in the OP group decreased(P<0.05),and there was no significant difference among NP group,NL group and OL group of the protein expression.(6)Results of HE staining in hippocampal CA1 area showed: Compared with NL group,NP group,and OL group,OP group HE showed that nerve cells were loosely arranged and the number of cells was significantly reduced(P<0.01).The morphology of nerve cells in hippocampal CA1 area of NL group,NP group and OL group was normal and arranged in order.Conclusion: Propofol anesthesia can cause long-term impairment of cognitive function in young obese rats.The mechanism may be related to the inhibition of Notch signaling pathway,which leads to the decrease of HO-1 and SOD1 enzyme activities,causing oxidative-antioxidant imbalance. |
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