| Objective:Intravenous anesthetic Ketamine, which can produce good analgesia without obvious respiratory depression, can be used to anesthetize burn operative patient or alleviate the pain of field wound, war and terminal cancer patients, but such side effects as cognitive dysfunction, . cardiovascular system excitement and hallucinogenic activity have limited its clinical application. However, the elderly patients have a high rate of cognitive dysfunction after operation, therefore, the use of ketamine may further increase the incidence of postoperative cognitive dysfunction in elderly patients. Intravenous anesthetic propofol can remarkably inhibit or eliminate ketamine's side effects including cardiovascular system excitement and hallucinogenic activity, and it has also a protective effect against neuron injuries. However, effect of propofol on short-term congnitive dysfunction induced by ketamine is still unclear. The present study aimed to investigate effect of propofol on the hippocampal neurons and cognitive function injuries induced by ketamine anesthesia in old rats. Methods:32 SD old rats were randomly divided into saline (NS), ketamine 40mg/kg/h (K), propofol 30 mg/kg/h (P) and ketamine 40mg/kg/h+propofol 30 mg/kg/h (PK). Intravenous infusion 2h/day for 7 days. 24h after the final infusion, rat's escape latency period and spatial search capability were record by Morris Water Maze, which were used to investigate behavior changes of rats receiving different medication. After Morris Water Maze, the rat was sacrificed and hippocampus tissue was harvested for paraffin section and the neuron apoptosis as well as caspase-3 protein expression were determined by TdT-mediated dUTP Nick-End Labeling (TUNEL) and immunohistochemistry respectively. Results:①Latency period(LP): Compared with LP of 1 or 2 day of NS group, no difference was found in P group(n=8, P>0.05), but LP of K, PK group were significantly prolonged (n=8, P<0.05); Compared with LP of 1 or 2 day of K group, LP of PK group was obviously shorten (n=8, P<0.05);Compared with LP of 3,4,5 day of NS group, LP of P, K, PK group was obviously prolonged (n=8, P<0.05); Compared with LP of P group, LP of PK group was also obviously prolonged (n=8, P<0.05); Compared with LP of K group, LP of PK group was obviously shorten (n=8, P<0.05).②Spatial search capability:The frequency across the original platform in group NS, P, K, PK was (6.75±1.98), (4.88±1.13), (1.88±0.83) and (3.38±1.19) respectively. The frequency through the original platform in group P, K, PK was lower than that in group NS (n=8, P<0.05); Compared with K group, the frequency through the original platform in group P, PK was obviously increased (n=8, P<0.05); The frequency through the original platform in group P was obviously higher than that in PK group (n=8, P<0.05).③Neuronal apoptosis:The apoptosis rate in group NS, P, K, PK was (1.09±0.21)%, (8.81±1.08)%, (20.42±5.68)% and (13.88±1.66)% respectively. Compared with NS group, the apoptosis rate in group P, K, PK was significantly increased (n=8, P<0.05); Compared with K group, the apoptosis rate in group P, PK was obviously decreased (n=8, P<0.05); Compared with P group, the apoptosis rate in group PK was obviously increased (n=8, P<0.05).④Protein Caspase-3 expression:The expression of Caspase-3 in group NS, P, K, PK was (2.41±0.70)%, (8.09±1.18)%, (17.00±2.11)% and (12.52±1.68)% respectively. Compared with NS group, Caspase-3 expression in P, K, PK group was obviously increased (n=8, P<0.05); Compared with K group, Caspase-3 expression in group P, PK was significantly decreased (n=8, P<0.05); Compared with P group, Caspase-3 expression in PK group was also obviously increased (n=8, P<0.05). Conclusions:①Propofol or ketamine alone can cause short-term cognitive dysfunction and the hippocampal neuronal damage in old rats, but the damage induced by ketamine was obviously higher than propofol.②Propofol can alleviate cognitive dysfunction and hippocampal neuronal damage induced by Ketamine anesthesia in old rats.
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