| Part One:Method of Rapidly Establishing Mild Cognitive Impairment Rat ModelsObjective:To explore method of rapidly establishing mild cognitive impairment models in rats by D-galactose(D-gal)and the appropriate dose.Method: Rats were divided into five groups randomly,20 in each group.The model group A,B,C,D were received hypodermic injection of D-gal with the concentration of 100,300,1000,2000 mg/(kg·d)respectively for 1 week,the control group received the same volume of saline.After injection,the Morris water maze(MWM)began,the first 5 days of MWM was place navigation test,at the sixth day,the 60 s spatial probe test was done.Then half rats of each group were drew at random,and after aneasthesed,they were cut off the head to take out the brain tissue on ice tray,then made into homogenate for detecting contents of the MDA,activities of SOD and concentration of ACh E via ELISA technology,and the pathomorphologic change of hippocampus was observed by HE staining on the rest rats.Result: 1.The survival rate of each group was 100%.Compared with control group,the weight of group D gained less and the swimming speed was lower.2.At day 2-5 of the place navigation test of MWM,the escape latencies of group C and D were prolonged than that of control group.In the spatial probe test,numbers of crossing the platform in 60 s of group C and D were 3.05±0.76 and 2.05±0.69,that of control group 4.40±1.05 significantly reduced(p<0.05).3.In group C and D,the levels of MDA were 29.19±2.35 ng/ml and32.57±2.05 ng/ml respectively,were higher than control group20.52±2.08 ng/ml(p<0.05).The levels of SOD of group C and D were1.46±0.12 IU/ml and 1.34±0.13 IU/ml respectively,were lower than control group 1.74±0.12 IU/ml(p<0.05).And the levels of ACh E of group C and D were 3.52±0.70 ng/ml and 4.02±0.39 ng/ml respectively,were higher than control group 1.72±0.33 ng/ml(p<0.05).4.The pathomorphologic change of hippocampus shows,in group C,several pyramidal cells lost,density of cell was slightly decreased,pyknotic nucleis increased and some pyramidal cells were dark-stained and a small amount of cell apoptosis in CA1 region of hippocampus,while cerebral white matter was normal.In group D,density of pyramidal cells were significantly decreased,arranged obviously loose and in a mess,more cells were condensed,dark-stained and apoptosis in CA1 region.Conclusion: Rats received hypodermic injection of D-gal with 1000 mg/(kg·d),conformed to the change of the pathology and characteristics of mild cognitive impairment model.Part Two: Influence of Different Concentrations of Sevoflurane on Cognition of Mild Cognitive Impairment Rat Models Induced by D-galObjective:To research the influence of different concentrations of sevoflurane on mild cognitive impairment rat models,preliminarily probed into the probable mechanism of sevoflurane affected postoperative cognitive function on these rats.Method: Rats received hypodermic injection of D-gal with 1000 mg/(kg·d)to establish models of mild cognitive impairment.Then Grouped according to random number table method after modeling,M0 inhaled100% O2(2 L/min)3h;M1 inhaled 2% sevoflurane and 100% O2(2L/min)3h;M2 inhaled 4% sevoflurane and 100% O2(2 L/min)3h.Inhalation stopped,take the caudal vein blood of each rat for gas analysis;After 24 hs,the MWM began,then half rats of each group were drew at random,and after aneasthesed,they were cut off the head to take out the brain tissue on ice tray,then made into homogenate for detecting contents of the A?1-42 and Tau via ELISA technology,and the pathomorphologic change of hippocampus was observed by HE staining on the rest rats.Result: 1.Every rats were waking up well,no death.Gas analysis shows no differences among groups on PH,Pa O2,Pa CO2,HCO3-(p>0.05).2.In the place navigation test of MWM,compared with group M0,the escape latencies of ereryday were not statistically significant in group M1(p >0.05),and that of group M2 has statistical significance(p<0.05).In the spatial probe test,compared with group M0 3±0.73,the numbers of crossing the platform in 60 s were not statistically significant in group M1 2.88±0.72(p > 0.05),and that of group M2 2±0.63 has statistical significance(p<0.05).3.Compared with group M0 26.53±3.38 ng/ml,the levels of A?1-42 were not statistically significant in group M1 28.77±3.06 ng/ml(p >0.05),and that of group M2 35.05±2.68 ng/ml has statistical significance(p<0.05).Compared with group M0 265.06±26.03 ng/ml,the levels of Tau were not statistically significant in group M1278.29±25.13 ng/ml(p > 0.05),and that of group M2 317.79±23.45ng/ml has statistical significance(p<0.05).4.The pathomorphologic change of hippocampus shows,in group M0,several pyramidal cells lost,density of cell was slightly decreased,pyknotic nucleis increased and some pyramidal cells were dark-stained and a small amount of cell apoptosis in CA1 region of hippocampus,while cerebral white matter is normal.In group M1,arranged loose,several cells were condensed,dark-stained and apoptosis in CA1 region.In group M2,density of pyramidal cells was significantly decreased,arranged obviously loose and in a mess,more cells were condensed,dark-stained and apoptosis in CA1 region.Conclusion: 1.Inhaled 4% sevoflurane may deteriorate the cognitive function of mild cognitive dysfunction rats.2.Sevoflurane may induced protein A?1-42 deposition and/or increased the protein Tau in the brain,therefore,it would adversely affect learning and memory ability of rats,damage its cognitive function. |
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