Effects Of Preconditioning With Nimodipine On Postoperative Cognition Disorders Of Aged Rats

Objective: To evaluate the effect of preconditioning with nimodipine on postoperative cognitive dysfunction of aged rats.Methods: Ninety health male Sprague-Dawley rats, aged 18 months, weighing 300-500 g, were randomly divided into 3 groups(n=30 eath) using a random number table: nimodipine control group(group N), surgery group(group S), and nimodipine + surgery group(N+S group). In group N and group N+S, rats were intraperitoneally injected with nimodipine(1mg/kg), 30 min later, group N only inhaling pure oxygen for 2 h, subsequent processing of group N+S was same with group S. Group S were intraperitoneally injected with same volume of saline with group N, 30 min later, rats of group S were anesthetized by inhaling 1.8 % isoflourane underwent splenectomy, anesthesia and operation time was 2 h. Morris water maze test was performed on 1 day before operation and 1st, 3rd and 7th days after operation. After the end of Morris water maze test at 1 day before operation and 1st and 7th days after operation, 10 rats were sacrificed and brains were removed and hippocampi were isolated for determination of apoptosis in hippocampal neurons, intracellular [Ca2+]i in cytoplasm, and hippocampal Bcl- 2 and Bax m RNA expression and the ultrastructure of hippocampal neurons. Measurement data were expressed as mean ± standard deviation, comparation using one-way ANOVA within-group and between groups, T test was used to compare groups within the groups, The difference was statistically significant according to P<0.05.Result:1 Morris water maze results: Compared with the preoperative, at each time point after operation, the escape latency and the number of crossing the original platform was no significant difference in group N(P>0.05),the rats of group S and group N+S on 1th, 3rd days after operation were prolonged the escape latency period and reduced the frequency of crossing the original platform(P<0.05); Compared with group N, the rats of group S and group N+S on 1th, 3th days after operation were prolonged the escape latency period and reduced the frequency of crossing the original platform(P<0.05); Compared with group S, the rats of group N+S were shortened the escape latency period and increased the frequency of crossing the original platform(P<0.05).2 The results of Flow cytometry test : Compared with the preoperative, group N on 1th and 3th days after operation, the apoptotic rate and intracellular [Ca2+]i of hippocampal neurons were no significant difference in group N(P>0.05); Compared with group N, the rats of group S and group N+S on 1th day after operation, the apoptotic rate and intracellular [Ca2+]i of hippocampal neurons were increased(P<0.05). Compared with group S, at each time point after operation of group N+S, the apoptotic rate and intracellular [Ca2+]i of hippocampal neuronal were decreased(P<0.05).3 The expression of Bcl-2 and Bax m RNA: Compared with preoperative, at each time point after operation, the hippocampal Bcl- 2 and Bax m RNA expression was no significant difference in group N(P>0.05); Compared with group N, the rats of group S and group N+S on 1th day after operation, hippocampal Bcl-2 and Bax m RNA had a higher expression, the Bax/Bcl-2 ratio was increased(P<0.05); Compared with group S, at each time point after operation of group N+S, the hippocampal Bcl-2 m RNA had a higher expression, the hippocampal Bax m RNA had a lower expression and the Bax/Bcl-2 ratio was decreased(P<0.05).4 The ultrastructure of hippocampal neurons: The ultrastructure of hippocampal neurons showed normal in group N; Group S on 1th day after operation, the hippocampal neurons nuclear was significantly condensed and side shifted, the mitochondria were fusion and disappeared, cytoplasm and endoplasmic reticulum were highly edema. On 7th day after operation, the hippocampal neurons nuclear were condensed and side shifted, mitochondria and cytoplasmic were edema; The rats of group N+S on 1th day after operation, the neuronal nuclear transfer were mild side shifted and condensed, mitochondria and cytoplasmic were light edema. On 7th day after operation, neuronal nuclear were light condensed and light side shifted, mitochondria and endoplasmic reticulum edema was not obvious.Conclusion: Nimodepine preconditioning can prevent postoperative cognitive function of aged rats, and inhibition of calcium overload induced apoptosis in hippocampal neurons may be involved in the mechanism.