Effect Of Icariside â…¡ On Ibotenic Acid-induced Learning And Memory Impairment In Rats

Objective: To investigate the effect of icariside Ⅱ(ICS Ⅱ)on learning and memory impairment induced by IBO.Methods: Male Sprague Dawley(SD)rats were randomly divided into 7 groups: Sham,Sham+ICS Ⅱ-H,IBO,IBO+ICS Ⅱ-L(4 mg/kg),IBO+ICS Ⅱ-M(8 mg/kg),IBO+ICS Ⅱ-H(16 mg/kg)and IBO+Donepezil(0.6 mg/kg).The IBO,IBO+ICS Ⅱ-L,IBO+ICS Ⅱ-M,IBO+ICS Ⅱ-H and IBO+Donepezil group were fixed on the stereotaxic instrument,a volume of 2 μL of IBO(2 μg/μL)solution was injected into the lateral ventricle by micro syringe at the rate of 0.4 μL/min and remained for 5 min.Sham group and Sham+ICS Ⅱ-H was injected same volume saline instead of IBO group.From the first day after surgery,animals were intragastricly administered with different doses of ICS Ⅱ,donepezil,or saline twice per day for subsequent 20 days.At the 12 th day,Morris water maze was used to test the learning and memory function for consecutive 9 days.Thereafter animals were sacrificed after anesthetized by 7 % chloral hydrate.Morphological examination was performed by hematoxylin-yihong staining,Nissl staining and TdT-mediated dUTP nick end labeling(TUNEL)assay.Furthermore,the expression of Bax,Bcl-2,Calbindin-D28 k proteins,the level of active-caspase-3,p-ErK,p-JNK,p-p38 were examined by Western blot respectively.Results: Compared with sham group,the average escape latency of rats in IBO group was significantly prolonged;the hippocampal neurons were degenerated and damaged seriously;the density of hippocampal neurons was decreased;the apoptosis of hippocampal neurons was increased significantly;the Bax expression and active-caspase-3,p-ErK,p-JNK,p-p38 level were significantly increased,while,the Bcl-2 and calbindin-D28 k expression were decreased;However,compared with the IBO group,the average escape latency of rats in IBO+donepezil or IBO+ICS Ⅱ-L,IBO+ICS Ⅱ-M,IBO+ICS Ⅱ-H group was shortened;the damage of hippocampal neurons were reduced;the density of hippocampal neurons was increased;the apoptosis of hippocampal neurons was decreased significantly;Furthermore,the ratio of Bax/Bcl-2 was reduced;the content of active-caspase-3 were decreased,the levels of p-ErK,p-JNK,p-p38 were decreased.While,the expressions of calbindin-D28 k protein was increased.Conclusion: ICS Ⅱ significantly ameliorates IBO-induced learning and memory impairment in rats,Effect of ICS Ⅱ maybe related with inhibition of neuronal degeneration,neuronal loss and neuronal apoptosis.