The Effect Of Piper Kadsura Ohwi On The Ethology Of AD Model In Rat

Background:Alzheimer's disease(AD) is a kind of neurodegenerative disease with progressive cognitive impairment as the main manifestation. Pathological characteristic of AD is the formation of senile plaques, neurofibrillary tangles and neuronal and synaptic loss in specific brain regions.β-amyloid (Aβ) is the main component of senile plaques. Althouth the definite etiological factor and the concrete pathogenesis of AD is not confirmed,hypothesis related to Aβargues that Aβ,mainly produced by the hydrolysis of Aβprecursor protein(APP),deposites in such structures as hippocampus and basal nucleus due to dysmetabolisism,thus initiate the pathological process of AD. Several researches found that Aβ1-42 oligomer is the main toxic form of AD,and has a more neurotoxic effect than fibrillar Aβ1-42 dose.The extent of cognitive impairment is related to the level of Aβ1-42 oligomer rather than the level of the total Aβamount.This study used Aβ1-42 oligomer and fibrillar Aβ1-42 to induce the cognitive impairment and analized the impact of the two forms of Aβ1-42 on the cognition respectively.Recently,many AD animal model have been used but none could completely simulate every aspect of AD including abnormality of biochemistry,pathology,behavior and cognition. Continuous intracerebroventricular infusion of AP could partly duplicate the pathological manifestation of AD,and a mount of Aβdistributes diffusely in the brain rather than resembles in the local injectional site.so animal administrated with continuous intracerebroventricular infusion of Aβcan act as animal model for AD research.Piper kadsura ohwi is thought to have anti-inflammation and neuroprotection function.Numerous researches published told us that continuous intracerebroventricular infusion of Aβcan induce the change of the ethology of AD model rat,but whether or not piper kadsura ohwi can improve these change isn't clear to us. So this sdudy is aimed at the effect of piper kadsura ohwi on the change of the ethology of Aβ-induced AD model rat. Therefore, it is important theoretical significance and potential applications to find the effective intervention measure. Objective:To explore the establishment of AD animal model in the way of continuous intracerebroventricular infusion of Aβ; To explore the impact of Aβ1-42 oligomer and fibrillar Aβ1-42 on the ethology of model rat;To explore whether or not piper kadsura ohwi can ameliorate the ethological changes.Methods:60 SD rats were randomly divided into 10 groups (n=6) and received continuous intracerebroventricular infusion of Aβthrough mini-osmotic pump:normal control group(A group,received no surgery and treatment),sham operation group(B group,received the implantation of infusion kit and mini-osmotic pump,no reagent),fibrillar Aβgroup(C group,received continouse infusion of fibrillar AP and methyl cyanides and TFA),fibrillar Aβand kadsura pepper group(D group, received fibrillar Aβand methyl cyanides and TFA,fibrillar Aβand DMSO(E group, received fibrillar Aβand methyl cyanides and TFA),methyl cyanides and TFA group(F group,received methyl cyanides and TFA,Aβoligomer group(G group, received Aβoligomer and HDL and HEPES),Aβoligomer and kadsura pepper group(G group,received Aβoligomer and HDL and HEPES),Aβoligomer and group(H group,received Aβoligomer and HDL and HEPES),Aβoligmer and DMSO group(I group,received Aβoligomer and HDL and HEPES),HDL and HEPES group(J group,received HDL and HEPES).After sugery, rats of D group and H group received intraperitoneal injection of 10% piper kadsura ohwi extract(containing 2.5% DMSO) everyday, 1ml per 100g weight,and as control groups, rats from E group and I group received intraperitoneal injection of 2.5% DMSO, 1ml per 100g weight.The treatment last 5 weeks. Morris water maze experiment began on the 31nd day after surgery,and comprised two phases—acquisition trials and probe trial.During acquisition trials, escape latency was recorded. During probe trial,real-time video was recorded,and the proportion of time and path spent in the target quadrant in which the hidden escape platform was previously located was noted,the times the rat swam through where the hidden escape platform was also noted.Results:(1) acquisition trials:escape latency was longer in G group than that in C group(P<0.05),and escape latency was longer in C group than that in F group(P<0.05), escape latency was longer in G group than that in J group (P<0.05);compared with C group and E group, the escape latency in D group was shorter(P<0.05); compared with G group and I group, the escape latency in H group was shorter (P<0.05); there was no significant difference between A group, B group, F group and J group.(2) probe trial:the times rat swam through where the hidden escape platform was in G group was less than that in C group, the proportion of time and path spent in the target quadrant in G group were lower than that in C group (P<0.05); the times rat swam through where the hidden escape platform was in C group and G group was less than that in F group and J group respectively (P<0.05), the proportion of time and path spent in the target quadrant in C group and G group were lower than that in F group and J group respecively(P<0.05);the times rat swam through where the hidden escape platform was in D group was more than that in C group and E group, the proportion of time and path spent in the target quadrant in D group were higer than that in C group and E group (P<0.05);the times rat swam through where the hidden escape platform was in H group was more than that in G group and I group, the proportion of time and path spent in the target quadrant in H group were higer than that in G group and I group (P<0.05); there was no significant difference between A group, B group, F group and J group.Conclusions:Continuous intracerebroventricular infusion of A(3 can establish AD animal model; Aβ1-42 oligomer had a more severe impact on the ethology of AD model rats than fibrillar Aβ1-42 did; piper kadsura ohwi may ameliorate the ethological changes of AD model rats.