Effect Of Propofol And Sevoflurane Combinations On Postoperative Cognitive Function Of Patients With MCI And Its Mechanism Of Oxidative Stress

Mild cognitive impairment?MCI?is a transitional state through which normal elderly people gradually develop Alzheimer's disease.Patients with MCI suffer from memory impairment that does not match their age and educational level,but the impairment does not affect their daily life nor reaches the diagnostic criteria for dementia.Patients with MCI are at high risk for conversion into Alzheimer's Disease?AD?.Therefore,perioperative intervention is particularly important to avoid or delay the development of MCI.Objective To evaluate the effects of different propofol and sevoflurane combinations on postoperative cognitive function of patients with MCI undergoing surgery and its mechanism of oxidative stress.Methods In clinical study part,one hundred and four patients of both sexes,aged 65-75yr,weighing 60-80kg,of American society of anesthesiologists physical status II or III,scheduled to undergo elective lower limb fracture surgery,were to be scored according to Montreal cognitive assessment?MoCA?,mini mental state examination?MMSE?,dementia scale?CDR?and daily living ability scale?ADL?to identify patients with mild cognitive impairment before the surgery.They were randomly assigned to 4 groups?n=26 each?using a random number table:propofol group?group P?,sevoflurane group?group S?and different ratios of medicine dosage for propofol and sevoflurane?group PS1,2?.The patents inhaled 1.3MAC sevoflurane in group S.The patents inhaled 0.7 MAC sevoflurane and TCI 1.2?g/ml propofol was infused intravenously in group PS1.The The patents inhaled 1.0 MAC sevoflurane and TCI 0.6?g/ml propofol was in group PS2.TCI 4?g/ml propofol was in group P.MoCA and MMSE were used to evaluate the cognitive function of patients 1d before the operation?T0?and 7d after operation?T1?.The plasma concentration ApoJ and?-syn related to cognitive function in blood samples,which were drawn from T₀ and T₁ would be measured.In basic study part,healthy male SD rats,aged 16¹8months,were used forestablishment of the cerebral hypoperfusion induced MCI models.Rats with MCl were divided into 7 groups?n=18 each?using a random number table:Normal Control group?group NC?,Control group?group C?,sham operation group?sham group?,sevoflurane group?group S?,propofol group?group P?and different ratios of medicine dosage for sevoflurane and propofol groups?PSl,2groups?.In sham group,the rats only cut the skin and exposed the sutured.The rats inhaled 1.3MAC sevoflurane in group S.The rats inhaled 0.7 MAC sevoflurane and20 mg·kg^-1·h^-11 propofol was infused intravenously in group PS1.The rats inhaled 1.0MAC sevoflurane and 10 mg·kg^-1·h^-11 propofol was infused intravenously in group PS2.40 mg·kg^-1·h^-1 propofol was infused intravenously in group P.The anesthesia time was 3h.After disappearance of righting reflex,open reduction and internal fixation was performed after tibial fracture was induced.7 days after operation,Y maze test and open-field test were used to assess the rats'cognitive function.Their hippocampal tissues were isolated to study the changes of NMDAR2B and DMT1levelsbywesternblotting.Ironcontentwasdetectedbythe Prussian blue staining and atomic absorption spectrophotometer.Results In clinical study part,compared with group S,the scores of MMSE and MoCA of the other three groups increased significantly in T₁?P<0.05?;Compared with group PS1,the scores of MMSE and MoCA of the group P and group PS2decreased significantly in T₁?P<0.05?;Compared with T₀,the score of MMSE and MoCA of group S,group P and group PS2 decreased significantly in T₁?P<0.05?.The incidence of POCD was 34.6%,0.77%,19.2%,23.1%,in group S,group PS1,group PS2,group P,respectively;The incidence of POCD was lower in group PS1than in the other three groups?P<0.05?.Compared with group S,the plasma concentration of ApoJ and?-syn in the other three groups decreased significantly in T1?P<0.05?.Compared with group PS1,the plasma concentration of ApoJ and?-synin group P and group PS2 increased significantly in T₁?P<0.05?.Compared with T₀,the plasma concentration of ApoJ and?-syn in group S,group P and group PS2increased significantly in T₁?P<0.05?.In basic study part,The results of Y-maze,western blotting and iron content showed that compared with group NC,the percentage of time spent in the N-arm was lower in group C?P<0.05?,DMT1 and NMDAR2B were less expressed?P<0.05?,and iron content was higher?P<0.05?.When 4 kinds of propofol/sevoflurane combinations were compared,the percentage of time spent in the N-arm of group S was significantly lower than that of the PS1group,group PS2 and group P?P<0.05?,while it was higher in group PS1 than that in group PS2 and the group P?P<0.05?;The DMT1 and NMDAR2B expression levels were significantly higher in the S group than that in the group PS1 group PS2 and the P group?P<0.05?,while they were significantly lower in group PS1 than those in group PS2 and group P?P<0.05?;The iron content of group S was significantly higher than that in group PS1,group PS2 and group P?P<0.05?,while it was significantly lower in group PS1 than that in group PS2 and group P?P<0.05?.Conclusions Combination of TCI 1.2?g/ml propofol and 0.7 MAC sevoflurane has less negative effect on postoperative cognitive function of patients with MCI undergoing surgery within 7 days.0.7 MAC sevoflurane combined with intravenous infusion of 20 mg·kg^-1·h^-1 propofol anesthesia had less influence on cognitive function of MCI rats after ORIF surgery.The increased expression of DMT1 and NMDAR2B,the accumulation of iron in the brain,the occurrence of oxidative stress were major mechanisms by which sevoflurane anesthesia leads to cognitive decline of MCI rats after ORIF surgery within 7 days.