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Impact Of Deferoxamine On Postoperative Learning And Memory Ability And Hippocampal Ferritin In Aged Rats

Posted on:2016-11-28Degree:MasterType:Thesis
Country:ChinaCandidate:D ZhuFull Text:PDF
GTID:2284330470463105Subject:Anesthesiology
Abstract/Summary:PDF Full Text Request
1. Implications and objectivePostoperative Cognitive Disfunction( POCD) is defined as postoperative brain dysfunction of normal human because of the influence of various factors of the perioperation, and the clinical manifestations are usually anxiety, attenuation of ability of learning, memory and language. The research has been an new hotspot for POCD, however, the mechanism that trigger POCD is still unclear, and one of the risk factors is age, and that the incidence of POCD increases with ageing. Our research aims to investigate the relation between the behaviour and the change of ferritin in aged rats after operation.There were researches had indicated that the disorder of iron metabolism would cause nervous system disease under the pathological circumstance. The operation has been introduced to stimulate excessive iron, and more free iron would catalyze oxidation reduction reaction and produce a toxic effect on the cognitive ability[1][2]. In order to explore the relation between the ferritin in hippocampus and the behaviour of aged rats,we used simulated human laparotomy operation in aged rats. Intraperitonea administration of deferoxamine before operation to analysis whether it could improve the ability of learning and memory of the aged rats after operation,and provides strong support for the correlation of the ferritin in the brain of aged rats on POCD.2. Materials and methodsThe male Sprague Dawley rats were obtained from Chongqing Institute of Traditional Chinese Medicine. The aged rats were 20-22 months old and weighed 515±30g. Young adult rats were 3 months old and weighed 275±23g. The rats were randomly divided into three groups including adult surgery group(n=20,Adult + S), aged surgical group(n=20,Aged+S), aged control group(n=20,Aged+C). All groups were consecutive maze training for six days before surgery. Laparotomy model was performed under chloral hydrate(0.005 ml / mg) Anesthesia intraperitoneal injection the day after finishing the maze training. Evaluating the ability of learning and memory by the experiments of latency and space exploration for each group 1, 3, 7 days after surgery. The three groups have 60 rats,and there were four rats from each group in total 12 rats were killed and was detected the ferritin content in hippocampus by western blot 1、3、7d after surgery.The healthy male Sprague Dawley rats selecting were 20-22 months old and were divided into four groups: deferoxamine group(DFO, n=20), saline group(NS, n=20), iron dextran 1week group(IDO1, n=20),iron dextran 2week group(IDO2, n=20). The four groups were respectively injected with deferoxamine(100mg/kg), saline(2ml/kg) and iron dextran(100mg/kg) through intraperitoneal injection for seven consecutive days before surgery. IDO1 group and IDO2 group were administrated the same dose of iron dextran(100mg/kg) via an intraperitoneal route for seven consecutive days before surgery, but the latter was done a week earlier. Then these groups continued to be administrated by intraperitoneal injection immediately after finishing the everyday training of water maze. The latency, space exploration experiments and expressing of the ferritin content in hippocampus were detected at 3、7d after surgery.3. Results3.1 Detection of the influence of surgery on SD rats’ the ability of learning, memory and expressing of the ferritin content in hippocampus: Compared with aged surgical group, the adult surgical and aged control group showed the shorter latency and more crossing numbers over the platform at 3th day after Maze test. However, compared with aged surgical group, the latency and space exploration times of adult surgical and aged control group were no significant difference at 1、7th day after laparotomy.3.2 Analysis of the ability of learning, memory and expressing of the ferritin content in hippocampa by intraperitoneal injection of deferoxamine and iron dextran on water maze:The average speed of four groups were roughly the same at 3、7 d after laparotomy(P>0.05). At 3d after surgery, Compared with DFO group, the latency of NS and IDO1 group was obviously extent, and space exploration times were significantly reduced(P<0.05). Compared with the NS group, the latency and space exploration times of IDO1 group was only a slight difference(P>0.05),however, IDO2 group showed the longer latency and more times in the space exploration. There are significant differences about expressing of the ferritin content in hippocampus in the rats of the deferoxamine and saline group except IDO1 group.3.3 Analysis of the expressing of the ferritin content in hippocampus in iron dextran 1week group(IDO1) and iron dextran 2week group(IDO2):Compared with IDO1 group, there were significant differences in hippocampal ferritin in IDO2 groups at 3、7 d after laparotomy.4. Conclusions4.1 The ability of learning and memory in aged rats was impaired by laparotomy.4.2 Laparotomy had little effect on the adult rats’ memory ability and the expressing of the ferritin content in hippocampa in the behavioral maze experiment and the ferritin content in hippocampus experiment.4.3 It could improve the ability of learning and memory administrated deferoxamine through intraperitoneal injection for seven consecutive days before surgery in aged rats. It had opposite effect by intraperitoneal injection of iron dextran.4.4 Administrated iron dextran through intraperitoneal injection for two consecutive weeks before surgery. It would aggravate the aged rats’ ability of learning and memory in aged rats via intraperitoneal injection of iron dextran for 2 week in advance before surgery, but it would not decline the ability of learning and memory at IDO1 group.
Keywords/Search Tags:Deferoxamine, iron dextran, aged rats, adult rats, ferritin, hippocampus, cognitive dysfunction
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