| Objective: To study the effects of eleutheroside (ETS) on quinaldinic acid-induced learning and memory impairment and the protection on hippocampal neurons in aging rats. To study the effects of ETS on ACh,Ch and CHE, NOS, SOD, Na+-K+-ATPase, MAO enzymatic activity and approach the mechanism of pharmacologic action of ETS on learning and memory impairment.Metholds:(1)The extract of ETS:The extract methold of ETS was by macroporous adsorptive resins (MAR).(2) Animal grouping and preparation of model:Total of 65 male Wister rats(10m)were checked by ethology bolting. All rats were randomized into 6 groups: model group (MG), low dose group (LDG),middle dose group(MDG),high dose group(HDG),Huperzine A group(Hup-AG),sham operated group(SOG). All groups anesthetized by chloral hydrate. After stereotaxis, the ageing models were builded by injecting QA(dissolved into PBS) 2μL into CA1 district of double slides of hippocampus in MG,LDG,MDG,HDG,Hup-AG group, the SOG group were injected the same volume of PBS.(3) Treatment:One week after operation, NS, ETS or Hup-A was given (ig) to rats for 4 w.The MG and SOG groups were given NS(2mL). The LDG,MGD and HDG groups were given ETS(50,100,200mg·kg-1).The Hup-A group were given Hup-A (0.3mg·kg-1).(4) Measurements:The learning and memory ability was measured by Morris water maze at 1 w after operation and 4w after treatment. The serum was collected from tail blood at 1w after operation and 4w after treatment and brain was removed at 4w after treatment. ACh,Ch and CHE, NOS, SOD, Na+-K+-ATP,MAO enzymatic activity were measured in serum and hippocampus homogenate. The changes of hippocampus neuron were observed by Nissl stain.Results:(1)First latence of jumping up to the platform and the errors on MDG and HDG were much less than these on SOG and MG by step down test(P<0.05 or P<0.01); Place navigation and errors on HDG and MDG and LDG were much less than these on MG by Morris water maze(P<0.05 or P<0.01). All were increased by doses.(2)CHE activity in hippocampus homogenate on treatment group had no significant difference compared with MG(P>0.05). The concentration of Ach on treatment group was significantly more than that on Hup-A(P<0.05 or P<0.01). The concentration of ACh was significantly less than that on Hup-A(P<0.01). ACh/Ch on treatment group was 2.47 times that on Hup-A,7.76 times that on MG,1.5 times that on SOG. All were increased by doses.(3) NOS activity on treatment group was significantly weaker than that on MG,had no difference with that on SOG. Na+-K+-ATP and SOD enzymatic activity were significantly power than that on MG.MAO activity on HDG was significantly weaker than that on MG.(4) Pyramidal cells in CA1 on HDG was in good condition.karyopyknosis was not obvious and pyramidal cells arrange in order.Nissl were abundant.Apical dendrite was as well as that on SOG.The amount of pyramidal cells on MDG was significantly more than that on MG,less than that on HDG and SOG. All were increased by doses.Conclusions:(1)ETS can obviously improve the learning and remembering ability on quinaldinic acid-induced aging rats.it can be enhanced by increasing doses.(2)It is suggestes that :The mechanism of ETS may be concern to: Activiting Ch acetylase,improving the synthsis of ACh,enhancing the efficiency of cholinergic nerve, regulating the active of NOS,coupling nervous activity and cerebral blood flow,targeting growth and plasticity of synapse,improving releasing of transmitter,activiting Na+-K+-ATP enzyme,regulating the excitability of nerve unit,inproving the quality of cerebration,enhancing activity of SOD,furthering the elinimation of oxygen-derived free radicals,prevanting damage and protecting nerve unit,maintaining plasticity of cholinergic nerve,inhibiting the activity of MAO,decreasing the metabolism of catechol amine,improving the ability of brain.
|
PDF Full Text Request