Effect Of Propofol,Ketamine And Gm1 On The Cognitive Function And The Expression Of Caspase-3 In Immature Rats

PART ONE EFFECT OF PROPOFOL ON THE COGNITIVE FUNCTION AND THE EXPRESSION OF CASPASE-3, BCL-2 IN IMMATURE RATSObjective: To investigate the effect of different doses of propofol on cognitive function and the expression of caspase3 and Bcl-2 in 17-18-day old rats.Methods: Thirty-two immature SD rats with an age from 17 to 18 days weighting 33-42g were randomly divided into 4 groups as follows: control group (NS) and 3 propofol groups (P50, P100, P200) which were administered intraperitoneally propofol of 50 mg/kg/day, 100 mg/kg/day and 200mg/kg/day in a bolus or divided doses respectively for 6 consecutive days. The control group received normal saline instead of propofol. The test of learning and memory were performed in morris water maze everyday at the 3th hour after the rats waked up form anesthesia. The animals were killed on the 6th day, the brain specimen were got, and the expression of Caspase-3 and Bcl-2 were detected by immunohistochemistry.Results: The learning ability and memory function of groups 100 mg/kg/day and 200 mg/kg/day were significantly depressed,the score of morris water maze test were lower than control group (P <0.05). The expression of caspase-3 was higher in groups P100 and P200 than groups NS and P50; the expression of Bcl-2 was lower in group P100 and P200 (P <0.05),compared with group NS.Conclutions: Propofol can affect the spatial cognitive function of immature rats when the dose higher than 50 mg/kg/day and the mechanism of which may through affecting the expression of Caspase-3 and Bcl-2 of neuron. PART TWO EFFECT OF PROPOFOL AND GM1 ON COGNITIVE FUNCTION AND THE EXPRESSION OF CASPASE-3 IN IMMATURE RATSObjective: To investigate the effects of multiple doses of propofol or /and GM1 on cognitive function and the expression of caspase-3 in 17-18-day old rats.Methods: seventy-seven 17-18-day immature SD rats weighting 33-40g were randomly assigned to one of the 7 groups(n=11 each) as follows: control group(NS) , propofol 50 mg/kg group(P50), propofol 100mg/kg group(P100), propofol 200mg/kg group(P200), GM1 10mg/kg group(G), propofol 100mg/kg and GM1 10mg/kg group(P100G),propofol 200mg/kg and GM1 10mg/kg group(P200G). Each group received intraperitioneally propofol of 50 mg/kg/day, 100 mg/kg/day, 200mg/kg/day, propofol of 100 mg/kg/day and GM1 10mg/kg/day, propofol of 200 mg/kg/day and GM1 10mg/kg/day in a bolus or divided doses respectively for 6 consecutive days. The control group received normal saline instead of propofol. The test of learning and memory were assessed by the morris water maze everyday at the 3th hour after the rats waked up from anesthesia. The animals were killed on the 6th day after the morris water maze test and the brain specimen were got, the expression of Caspase-3 were detected by immunohistochemistry and western-blotting.Results:There was no significant difference in the result of water maze test and the expression of caspase-3 between control group and group G, P50.The latency period and swimming distance of water maze test were significantly longer in groups P100, P200 and P200G than in control group,the number of crossing the platform were fewer in above 3 groups (P <0.05). The swimming distance of water maze test in group P100G was longer than in control group(P <0.05). The expression of Caspase-3 was higher significantly in group P100, P200 and P200G, compared with group NS(P <0.05).Conclusions: Propofol 100 mg/kg/day and 200 mg/kg/day can decreases spatial cognitive function in immature rats, and GM1 can improve the disfunction, the mechanism of which may be through affecting the appotosis of neuron by regulating the expression of Caspase-3. PART THREE EFFECT OF KETAMINE ON THE COGNITIVE FUNCTION AND THE EXPRESSION OF CASPASE-3 IN IMMATURE RATSObjective: To study the effect of multiple doses of ketamine on cognitive function and the expression of caspase-3 in 17-18-day old rats.Methods: Twenty-two immature SD rats with an age from 17 to 18 days weighting 33-42g were randomly divided into 2 groups as follows: control group (NS) and Ketamine group(Keta) which were administered intraperitoneally Ketamine of 50 mg/kg/day, in a bolus dose respectively for 6 consecutive days. The control group received normal saline instead of Ketamine. The test of learning and memory were performed in Morris water maze everyday at 3th hour after the rats waked up form anesthesia. The animals were killed on the 6th day and got the brain specimen, the expression of Caspase-3 were detected by immunohistochemistry and western-blotting.Results: In the Morris Water Maze test, the latency period and the swimming distance of the group ketamine was significantly longer than in control group , the number of crossing the platform was fewer than in control group (P <0.05). The learning and memory ability were effected significantly by ketamine 50 mg/kg/day. The expression of Caspase-3 was significantly higher in group ketamine than in group NS (P <0.05).Conclutions: The ketamine can lead the spatial cognitive function impairment in immature rats when the dose is 50 mg/kg/day and the mechanism of which may be through affecting the apoptosis of neuron.