Effects Of Qidantongmai Tablet On Vascular Cognitive Impairment Of Rats With Chronic Cerebral Ischemia

Research background and purpose:Vascular Cognitive Impairment is one of the diseases which seriouslythreatened human health. It has some clinical characteristic in such as highincidence of a disease, Occult diseases, Progressive increase and long attacktime. Chronic cerebral ischemia is a key factor of Vascular CognitiveImpairment. At present, research results show that chronic cerebral ischemiamay cause disease and changes such as energy metabolism disorder, glucoseutilization reducing, neurotransmitters changing, Cerebral White Matter Damageand neuron loss and so on. The changes are the pathophysiological basis ofcognitive dysfunction that chronic cerebral ischemia result in, in which neuronloss has some relationships with oxidative stress, immunity and inflammation,cell apoptosis. MAD and SOD is the key indicator which reflects resistance to oxidative stress mechanism, caspase-3is key protease of cell apoptosis, it can beused as therapeutic target of ischemic brain injury.For modern medicine, this type of disease cure is done from every aspectand every mechanism, but clinical effects are not good. Therefore at present,early prevention and cure are main rule of this disease.Modern medicine research shows that traditional Chinese medical sciencehas some advantages of multi-target and multi-means, therefore, which has somemerits in the side of early prevention and cure. Though no Vascular cognitiveimpairment name be used, but some relevant descriptions of cause of diseaseand illness condition, which belong to disease areas of amnesia, dementia, Godstaying, syndrome and feeblemindedness. Spinal cord due to kidney deficiencyis the basic reason vascular cognitive impairment, and the same time, Bloodstasis and phlegm blockade, Qi Deficiency and Blood Stasis are its pathogenesis.QiDanTongMai Tablet (QDTMT) is Traditional Chinese Medicine Compound itdefer to Qi in traditional Chinese medicine theory, which has some effects ofSupplementing Qi and activating blood circulation and Wenjing and freeing.Previous clinical and experimental study shows that QDTMT has some effectsof Improved myocardial blood supply and Reduces myocardial infarct size,which has some effects for Acute cerebral ischemia-reperfusion injury, butresearch of Chronic cerebral ischemia has no been done. Therefore, thisexperiment uses permanent rats with ligation of bilateral common carotidarteries as chronic cerebral ischemia model. For the first time, this thesis studiesthe effects of QiDanTongMai Tablet (QDTMT) on the learning and memoryabilities of rats with chronic cerebral ischemia and explores its mechanismsfrom suppressing oxidative stress and inhibition of apoptosis. Methods and Contents:56Male-SD rats were devided into seven groups as follows: normal group,control group, model group, sham operation, low dosage QDTMT, moderatedosage QDTMT, high dosage QDTMT, and Nimodipine group,8rats for eachgroup. Except Vacuity contrast group and Sham group, the rats of other groupshave been manufactured as chronic cerebral ischemia model with2-V0method,and then been fed about two days. From the beginning of the third day, all ratswill be made ntragastric and medicine, all rats of the sham operation group andmodel group are injected saline solution about10ml/kg/d. all rats of theQDTMTL, QDTMTM, QDTMTH groups are injected QDTMT about0.36g/kg/d,1.08g/kg/d,3.24g/kg/d respectively. All rats of the Nimodipinegroup are injected Nimodipine6mg/kg/d, mixed saline solution to makeintragastric one time each day, and28days be done continuously, after28days,The Morris maze navigation experiment and space exploration experiment aremade to observe changing of learning and memory abilities of chronic cerebralischemia rats. And then,2rats are used to make Brain sections and HE stainingto observe changes of hippocampal neuron morphology. Other6rats are takebrain and brain protein immunohistochemical method is used to detect level ofSOD and MDA. Wester-blot is used to detect express of Hippocampal activityCaspase-3.Results:1. All rats made Morris water maze place navigation in the first day andsecond day, there were no significant differences for average escape latency ofall rats, while from beginning of the third day, there are clear distinction for ratsavoiding latency of control group, model group and treatment group. Ratsaverage escape latency of all treatment groups appreciably reduce. Among which effect of high dosage QDTMT is the best, its curative effect is close tocontrol group2. Water maze spatial probe experiment shows that it after5days swimmingtraining affects memory ability of rats. The experiment results show that thereare significant differences among the spatial rats memory ability of all groups,compare with normal group and sham group, residence time of target quadrantslowed dramatically for normal group (p<0.05), residence time in targetquadrant of all QDTMT groups than those of the model group, in which,residence time of target quadrant of high dosage QDTMT is more.3. HE strain: for model group, hippocampal neurons CA1area shows typicalneuropathic changes, number of hippocampus neurons cell reduces, but nomyocardial infarction emerges. For control group and sham operation, structureand neuron size and neuron arrange of hippocampal neurons CA1area is normal.Drug disposition improves significantly organization framework of hippocampalneurons CA1area ischemia in rats, in which, high dosage QDTMT group hasthe best curative effect.4. MDA and SOD levels of hippocampal: for model group, in rathippocampus, SOD activity drop significantly, MDA level increased obviously.SOD activity cerebral ischemia rats hippocampal area is significantly higherthan model group of those after medicine. In among, high dosage QDTMTgroup has obvious effect, which is close to Nimodipine group, middle and lowdosage QDTMT group inferior to high dosage QDTMT group.5. Caspase-3level of hippocampal activity show: For model group, activecaspase-3expression of hippocampal parts apparently increases. Activecaspase-3expression of hippocampal parts decreased significantly after cure forall cure groups. Effect of high dosage QDTMT group is better than those of low and middle dosage QDTMT group, and it is close to control group.Conclusions:1. QDTMT can improve the vascular cognitive impairment of chronic cerebralischemia, High dosage QDTMT is the best, which shows this medicine can beused to protect chronic cerebral ischemia.2. QDTMT can reduce MDA level and increase SOD active of rathippocampus of chronic cerebral ischemia, which shows that QDTMT canimprove learning of chronic cerebral ischemia by reducing oxidative stress levelof hippocampus area and protect hippocampus neurons.3. QDTMT can degrade obviously hippocampus area active caspase-3expression, which shows it can improve improve learning of chronic cerebralischemia by reducing cell apoptosis and protect hippocampus neurons.