Effect Of Exendin-4on Postoperative Cognitive Function Of Aged Rats After Splenectomy

Objective To examine the effects of Exendin-4(Ex-4), an analogue of glucagon-like peptide-1(GLP-1), on beheavior, blood glucose and neuroinflammation in aged rats after splenectomy. To investigate the effect of Ex-4on postoperative cognitive function of aged rats after splenectomy and its mechanism.Methods Male Sprague-Dawley rats,22-24weeks, weighting500-700g, were used in the study. Forty-eight healthy aged rats were randomly divided into four groups (n=12for each group):control group (group C), Ex-4group (group E), operation group (group O) and operation plus Ex-4group (group OE). Group C and E did not receive anesthesia nor splenectomy, Group O and OE received splenectomy under neuroleptic anesthesia (intraperitoneal injection of20μg/kg fentanyl and500μg/kg droperidol). Group E and group OE received an intraperitoneal injection of5μg/kg both in preoperative minute30and postoperative hour12; group C and group O received an intraperitoneal injection of the same dose normal saline at the corresponding time. All rats performed the following measurements:(1) Morris water maze tests were performed on preoperative day1-6and postoperative hour24. Learning and memory function were evaluate by Escape latency (EL) and swimming total distance (STD).(2) The fasting blood glucose on preoperation, postoperation and postoperative hour24was measured.(3) All the rats were executed after the Morris water maze tests were performed on postoperative hour24. The expression of IL-1β in hippocampus was measured by western blot analysis. The expressions of Glial fibrillary acidic protein (GFAP) were measured by immunohistochemical assay.Results:(1) Morris Water Maze:On preoperative day4-6, there was no significant difference was found in EL and STD among groups (.P>0.05). On postoperative hour24, there was no significant difference in EL and STD between group C and group E(P>0.05). EL and STD of group O and OE increased compared with those of group C (P<0.05). EL and STD of rats in group OE was decreased compared with those of group O (P<0.05).(2) Fasting blood glucose:There was no significant difference was found in preoperative blood glucose among groups (P>0.05). Compared with group C, blood glucose had no significant differences in postoperative and postoperative hour24in group E (P>0.05) and the postoperative blood glucose of rats in group O and group OE significantly increased (P<0.05). Compared with group O, the postoperative blood glucose of rats in groups OE significantly decreased (P<0.05). Compared with preoperation, fasting blood glucose was significant increase in postoperative and postoperative hour24between group O and group OE (P<0.05). There was no significant difference was found in postoperative and postoperative hour24in group O (P>0.05), Compared with postoperation, fasting blood glucose was significant decreased in postoperative hour24in group OE (P<0.05).(3) Expression of IL-1β in hippocampus:Compared with group C, the expression of IL-1β was significantly increased in rats of group O and group OE(P<0.05) and there was no significant difference was found in group E. Compared with group O, the expression of IL-1β was decreased significantly in group OE (P>0.05).(4) Expression of GFAP in hippocampus:Compared with group C, the expression of GFAP in the hippocampal (CA1, CA3, DG) was significantly increased in rats of group O and group OE (P<0.05). and there was no significant difference was found in group E. Compared with group O, the expression of GFAP was decreased significantly in group OE (P>0.05).(5) Analysis of correlation:IL-1β correlated positively with postoperative24hour fasting blood glucose (r=0.814, P<0.001).EL and STD correlated positively with postoperative24hour fasting blood glucose (r=0.621,0.581; P=0.001,0.003). During peroperative period, EL and STD correlated positively with the changes in fasting blood glucose (r=0.75,0.872; P<0.001). Conclusions Ex-4can alleviate the postoperative cognitive function dysfunction of aged rats by inhibiting hippocampal neuroinflammation and stabilizing perioperative blood glucose.