Effects Of Tanshinone ?A Sulfonate On AD Model And Its Mechanism

ObjectiveIn order to obtain the pathological model of Alzheimer's disease by scopolamine intraperitoneal injection,to investigate tanshinone ?A sodium sulfonate(STS)to study the effect and mechanism of behavior of AD model mice,and provide a new Drug for clinical prevention and treatment of AD.Methods50 Male Kunming mice(KM),were randomly divided into control group(saline group 0.9%,n=10),scopolamine group(SCOP,SCOP:3 mg/kg,n=10),STS low dose group(group STSL,SCOP:3 mg/kg+STS:10 mg/kg,n=10),STS group(STSH,SCOP:3 mg/kg+STS:20 mg/kg,n=10),positive control group,donepezil(DON,SCOP:3 mg/kg+DON:3 mg/kg,n=10).Orally treated with saline,STS and donepezil for two weeks,scopolamine was intraperitoneal-injectionede for one week from the beginning of the eighth day,in the fourteenth day given scopolamine after the 0.5h water maze test.After Mirrors maze test,All mice were anesthetized,then the hippocampus and cortex were stripped on the ice-plate.ROS,MDA,SOD kit for determination of oxidative stress index,CHAT and ACTH kit to detect the cholinergic system index,WB was used for detected the expression of Bcl2 protein and TUNEL was used for detection apoptosis of hippocampus and cortex.ResultsDuring the 4 days of training,the time of finding the hidden platform decreased gradually.Compared with the blank control group,the SCOP group was markerly longer than the control group.However,the treatment of low dose low(10 mg/kg)and high dose(20 mg/kg)compared with the SCOP group the escape latency was shortened STS and donepezil.Displays the corresponding swimming path each fourth days:the SCOP group reflects the clutter and swimming path longer,giving STS and donepezil can significantly improve the situation.On the fifth day,the mice were removed from the platform to explore their free working space.Group SCOP showed a longer latency(20.2±2.3seconds),through the removal of position less platform(2.9±1.62),the time spent in the target quadrant(13.4±4.1 seconds),the less,given STS and donepezil can significantly improve the situation.These results indicate that STS treatment can significantly reverse the cognitive impairment and cognitive dysfunction in mice induced by SCOP.SCOP can be significantly increased in hippocampus(1.43±0.19%)and cortex(1.41±0.17%)AchE activity,suggesting that the cholinergic nervous system dysfunction may leads to learning and memory declined,and significantly reduced in STS after treatment and donepezil acetylcholinesterase activity.And SCOP can be significantly decreased in the hippocampus(0.48±0.07%)and cortex(0.27±0.09%)CHAT activity were significantly increased in the given STS and CHAT activity after donepezil treatment.Therefore,STS can improve the function of SCOP induced cholinergic related enzymes.In the model group,the ROS(4±0.41%and2.96±0.05%)and MDA(3.02±0.44%and 2.52±0.17%)in the hippocampus of the model group were significantly increased,and the SOD activity(0.38±0.11%and 0.47±0.16%)was significantly lower in the model group.Compared with the SCOP group,after STS administration and sent together to donepezil hydrochloride,MDA and ROS activity was significantly lower,and significantly increase the activity of SOD.Therefore,STS can improve the Cognitive decline caused by SCOP by improving the oxidative stress state.The model group can significantly increased the pro apoptotic protein Bax in hippocampus and cerebral cortex of model mice(2±0.12%and 1.82±0.08%)and caspase-3 protein(1.44±0.07%and 2.87±0.12%)expression,decrease the expression of Bcl-2(0.48±0.1%and 0.94±0.02%).Compared with the SCOP group,after STS administration and donepezil hydrochloride group together,can significantly increase the Bcl-2 protein,and downregulation the expression of Bax and Caspase-3 protein.This suggests that STS can improve the learning and memory impairment caused by SCOP by improving cell apoptosis.Compared with the control group,apoptosis of hippocampal neurons SCOP mice increased significantly;compared with group SCOP,STS and donepezil hydrochloride significantly decreased apoptosis of nerve cells.These results indicate that STS can improve SCOP induced neuronal apoptosis.ConclusionThe spatial learning and memory ability of 1 sodium tanshinone A sulfonate can improve the mouse hippocampus induced by scopolamine,and sodium tanshinone A sulfonate(20mg/kg)than the high dose of sodium tanshinone A sulfonate(10mg/kg)low dose effect is better.Tanshinone ? A sodium sulfonate and its improve mice spatial learning and memory disorder and brain function may reduce oxidative stress and improve the cholinergic system,inhibit neuronal apoptosis in steady state.STS can significantly can significantly increase the Bcl-2 protein,and downregulation the expression of Bax and Caspase-3 protein.This suggests that STS can improve the learning and memory impairment caused by SCOP by improving cell apoptosis.