Effects Of Ptat-xiap On The Behavior And Neuronal Oxidative Stress Injury In Rat Model Of Alzheimer’s Disease

Objective:To research the change of XIAP expression in neurons, and the effects of PTAT-XIAP fusion protein on the nerve cell apoptosis induced using A β (25to35) and its molecular mechanism, rat model of AD was established by Combined application of Aβ (25to35) with D-gal.Methods:Using the method of Morris water maze screening experimental animals, only40rats which escape latency less than120s are used in the experiment, randomly divided into four groups and each group10only.A (3model group:brain stereo controller is equipped positioning, every side in the hippocampus injected A β (25to35)2μ L (5g/L);A β joint D-half of lactose compound model group:according to the method of Aβ model group bilateral hippocampus were injected with Aβ, beginning with A (3injection28days before, intraperitoneal injection with D-half of lactose (50mg/kg/D)once a day, continuous42days;The treatment group:the hippocampus were injected with A β (25to35)5weeks after the rats tail intravenous injection of TAT-XIAP fusion protein (10mg/kg), twice A week for four weeks, Aβ model group rats tail intravenous injection of saline as equal drug control.The control group:bilateral hippocampus were injected with the same amount of saline.Made after the mold(after the injection of Aβ)8weeks, through the Morris water maze method observed the change of AD model rats behavior and learning and memory capacity,after the water maze experiment, take the eyeball blood, the hippocampus and the brain cortex.Detection rats total Superoxide dismutase(TSOD),Glutathione peroxedase(GSH-PX), malondialdehyde(MDA)content with the hydroxyl amine method and the colorimetric method;With RT-polymerase chain reaction (PCR) detection AD model big rat hippocampal and cortex in half tyrosine-methionine-aspartate-aspartate protease-3(Caspase-3) mRNA, XIAP mRNA expression;Make brain tissue paraffin slice, do HE dyeing understand AD in the rat model neurons the structural change;Do immunohistochemical, research Caspase-3protein in the AD in the rat model expression of neurons.The statistical analysis SPSS18.0application software, with P<0.05said a statistically significant difference.Results:1、Behavior changes:the rats activities and fight in A (3(25to35) and D-half of lactose composite senile dementia rat model is more than that in normal control group rats, and compound model rats of behavior change is more apparent than that in A (25to35) group.2、Morris water maze swimming results show that, Rats search and find security platform of the incubation period and escape route between each group swimming are significantly different.3、HE dyeing results show that,Aβ model group, composite model of neurons in the hippocampus and cortical have obviously cells damaged than control group;Compound model rats of neurons in the hippocampus and cortical cell damaged is more remarkable than that in Aβ (25to35) group;PTAT-XIAP treatment group of the hippocampus cortical neurons is more higher than that in Aβ model group, the number of damaged cells are reduced than that in Aβ model group, cells form relatively normal structure.4β Immunohistochemical, according to the results, active Caspase-3protein expression of Aβ model group and compound model group are higher than that in the control group; Active Caspase-3protein expression of compound model group is higher significantly than that in Aβ (25to35) group; PTAT-XIAP Caspase-3protein expression of treatment group is lower than that in Aβ model group.5RT-PCR results show that A β model group, compound model group compared with control group, XIAP mRNA in rat hippocampal and cortical tissue of each model group are significantly reduced, and Caspase-3mRNA level have obviously increase;compound model group compared with Aβ model, XIAP mRNA level in the hippocampus of cortical tissue are obviously reduced, Caspase-3mRNA level are raised obvious.6、Serum TSOD, GSH-PX, MDA tests showed that, Aβ model group, compound model group TSOD, GSH-PX vitality is lower than that in the control group, and MDA vitality in the control group is improved;TSOD, GSH-Px vitality of composite model group are lower significantly than that in Aβ model group, MDA vitality of A β model group is increased significantly; TSOD, GSH-Px vitality of the treatment group are higher significantly than that in A0model group, and MDA vitality is lower significantly than that in Aβ model group.Conclusions:This experiment successfully constructed rat AD model, and the results indicated that Aβ(25to35) can lead to memory impairment in the rat AD model significantly, and compound model combined A (3(25to35) with D-gal can better copy AD model; Aβ (25to35) can inhibit XIAP mRNA expressions and increase Caspase-3mRNA expressions, activate Caspase-3; Aβ (25to35) can also reduce serum TSOD and GSH-Px activity in rats AD, and increase the MDA content; PTAT-XIAP fusion protein can improve the memory impairment in rat AD model induced by Aβ(25to35).