Effect of nimodipine pretreatment on postoperative cognitive function in diabetic rats

Abstract

Objective To evaluate the effect of nimodipine pretreatment on postoperative cognitive function in diabetic rats. Methods One hundred and eighty healthy male Wistar rats, aged 3-4 months, weighing 260-310 g, were divided into 6 groups (n=30 each) using a random number table method: operation group (O group), diabetes mellitus group (DM group), diabetic cognitive impairment group (DCI group), nimodipine plus operation group (N+ O group), nimodipine plus diabetes mellitus group (N+ DM group) and nimodipine plus diabetic cognitive impairment group (N+ DCI group). Diabetes mellitus model was established by intraperitoneal injection of streptozotocin 55 mg/kg.Nimodipine 1 mg/kg was intraperitoneally injected at 6 weeks after establishing the model in DCI and N+ DCI groups and at 2 weeks after establishing the model in DM and N+ DM groups, and laparotomy was performed under sevoflurane anesthesia at 30 min after the end of administration.Morris water maze test was performed at 1 day before operation and 3 and 7 days after operation.Then rats were sacrificed, and hippocampal tissues were taken for determination of the apoptotic rate of neurons, cytoplasmic calcium concentrations (by flow cytometry) and expression of caspase-3 in hippocampus (by Western blot). Results Compared with the baseline at 1 day before operation, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, the apoptotic rate of hippocampal neurons and cytosolic calcium concentrations were increased, and the expression of caspase-3 was up-regulated at each time point after operation in six groups (P<0.05). Compared with group O, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, the apoptotic rate of hippocampal neurons and cytosolic calcium concentrations were increased, and the expression of caspase-3 was up-regulated at each time point after operation in DM and DCI groups (P<0.05). The escape latency was significantly shortened, the number of crossing the original platform was increased, the apoptotic rate of hippocampal neurons and cytosolic calcium concentrations were decreased, and the expression of caspase-3 was down-regulated at each time point after operation in group N+ DM as compared with group DM and in group N+ DCI as compared with group DCI (P<0.05). Conclusion Nimodipine pretreatment can improve postoperative cognitive function in diabetic rats, and the mechanism may be related to inhibiting calcium overload-induced apoptosis in neurons. Key words: Nimodipine; Diabetes mellitus; Cognition disorders