The Treatment And The Possible Mechanism Of Sesamin With Vitamin E Combination For Alzheimer’s Disease Rats

Objective: To study the sesamin combination with vitamin E for alzheimer’s diseaserats to see if there is a certain therapeutic effect, and to explore its possible mechanism.Method: Choose normal SD rats, blank controls(n=15) were developed by eitherintraperitoneal or intragastric administration of normal saline(NS ip,NS ig), and therest were induced by intraperitoneal injection D-galactose (D-gal) in the dose of180mg/(kg.d) combined with intragastric administration aluminium trichloride (AlCl3) inthe dose of15mg/(kg.d).After12weeks, Morris water maze was used to determine thesuccessful model rats that were subsequently randomized into AD model group (NS ip,D-gal ip+AlCl3ig), sesamin group (Ses160mg/kg.d-1; D-gal ip+AlCl3ig), vitamin E(VitE10mg/kg.d-1; D-gal ip+AlCl3ig) as well as sesamin with vitamin E combinationgroup (Ses160mg/kg.d-1+VitE10mg/kg.d-1; D-gal ip+AlCl3ig)(n=15for eachgroup).After consecutive8weeks of drug adminstration,Morris water maze was againused to test of rats the learning and memory ability of rats. The change of rathippocampal neurons was detected with Nissl staining. Bielschowsky staining was usedto observe rat hippocampal tangles.The NO levels were examined in rat cerebrospinalfluid and hippocampus homogenate by Griess Reagent method. Immunohistochemicalstaining was used to determine the expression of nitric oxide synthase (nNOS) and glutamate (Glu) protein at hippocampal neurons.At last,western blot method was usedto detect the expression of Aβ deposition,Tau and nNOS, NMDA receptor subunits（NR1, NR2A and NR2B) at rat hippocampal.Results:(1) As compared with the normal control group, the escape latency of ADmodel rats obviously were delayed and times of crossing the platform were reduced sothat learning and memory function ability was decreased significantly; Compared withmodel group, sesamin, vitamin E and sesamin with vitamin E combination can shortenthe AD rat escape latency, increase the number of crossing platform, improve the abilityof learning and memory.(2) As compared with the normal control group, the AD modelrats hippocampal occur within Aβ deposition, Tau protein content increasing andneurons lacking of nissl bodies and tangles; Compared with model group, sesamin,vitamin E and sesamin with vitamin E combination can effectively reduce the AD andAβ deposition, Tau protein content in hippocampus neurons lack of nissl body, improvethe tangles, play a role in treatment of hippocampal tissues.(3) Compared with normalgroup, and cerebrospinal fluid AD model rats obviously increase the NO content inhippocampus; Compared with model group, sesamin, vitamin E and sesamin withvitamin E combination can reduce the NO content of cerebrospinal fluid and thehippocampus in the AD rats.(4) Compared with normal group, the AD model ratshippocampal neuronal nitric oxide synthase (nNOS) and glutamate (Glu) positive cellsexpressing obviously increase; Compared with model group, sesamin, vitamin E andsesamin with vitamin E combination can effectively reduce nNOS and Glu positivecells expression at hippocampal in AD rats.(5) Compared with normal group, NMDAreceptor subunits NR1, NR2A and NR2B protein expression significantly increase inthe AD model rats. compared with model group, sesamin, vitamin E and sesamin withvitamin E combination can effectively reduce the protein expression of NMDA receptorsubunits NR1, NR2A and NR2B in the AD rats.Conclusion: sesamin, vitamin E and sesamin with vitamin E combination can improve the learning and memory ability of AD rats, decrease the Aβ deposition andhippocampus neurons lacking of nissl bodies, cut the Tau protein in hippocampus,improve tangles, and can reduce the NO content in the cerebrospinal fluid and thehippocampus, the effect of sesamin with vitamin E combination is better than that ofsesamin and vitamin E alone. The potential mechanism may be that (1) decrease ofnNOS positive cells and protein expression, reduce the NO synthesis;(2) reduce Aβprotein deposition and NMDA receptor subunits NR1, NR2A and NR2B proteinexpression at the hippocampus in AD rats;(3) cut the expression of Glu positive cells,NMDA receptor subunits NR1, NR2A and NR2B protein expression at thehippocampus in AD rats.