Effects Of Nimodipine On The Brain Tissue NO And AchE Of AD Rat Model

Purpose:Nimodipine (NIM), which has a chemical name of 2,6-dimethyl-4-(3-nitryl benzyl)-1,4-dihydro-3,5-quinolinic acid-2-armor oxygen ethyl-(1-armor ethyl), is a 1,4-dihydro pyridine class calcium channel antagonist compound. The NIM can easily penetrate the blood brain barrier. Because the cerebrum seahorse, the cerebral cortex, cerebral ganglion all contain high density dihydro pyridine combining site, NIM is possibly a better cure to Alzheimer disease AD than other kind of calcium antagonist compound. NIM can effectively improve the pathological state and prevent damage caused from "the calcium overload" of the cell. The animal experimentation proved that it can increase animal's inquisition behavior and improve, study and memory function. The clinical trial proved that NIM can significantly improve patient's memory, cognition and language competence, meanwhile, reduces ataxia, walking difficulty and abnormal behavior, and improve mood condition and sleep situation.In 1994 Khachaturian proposed the AD calcium stable state theory, which believes that the continuing elevate of cell calcium ion (Ca 2+) density will cause damages and perishes of the nerve cells. The cell culture and animal experimentation all proved that the instability of Ca 2+is concerned with AD pathology characteristic. High Ca 2+may activate the nitrogen oxide synthase to produce nitrogen monoxide (nitric oxide NO), which further participate in the AD brain cell death process as a free radical. Experimentation also proved that NO in the seahorse is closely related to study and memory. In vascular dementia (VaD), the NO density of cerebrospinal fluid and the dementia degree are positive related. Because NO is related to many kinds of pathology and physiological action in central nervous system, and creates a vicious circle with Ca2+elevates, which is the elevation of Ca 2+promotes the production of free radical, and then the free radical production aggravates the Ca 2+stack. Therefore, active control of this vicious circle provides a possible way to AD cure.Clinical experiences also found that the AD patients present cholinergic nerve function deficiency. Laboratory discovered that damage cholinergic nerve can successfully create AD model. Therefore, we concluded that central cholinergic nerve plays a vital role in study and memory process, also, the cholinergic neuron's degeneration is an important factor in creating AD. So the present treatment for senile dementia is mostly cholinergic medicine. Because Ca 2+is playing the vital role in the nerve physiology and transmission, reconstructs of Ca 2+stable may be helpful in the restoration of central cholinergic nerve.This experiment is for the purpose of using NIM to treat AD. Through observing the difference of each group experiment rats'brain organize NO and AchE content, and the Morris maze experiment comparison, after discussing the possibility of NIM treatment on AD and reconstruction of the Ca 2 +stable state, and the change of NO, AchE content, we infer that after re-balancing Ca 2+, NIM's further function is related to the content of NO and AchE.Method:Taking 40 health Wistar male rats stochastically, and carrying on the labyrinth training before the grouping, and recording and comparing the data before and after touring the labyrinth. Taking 20 successful AD rats model according to the labyrinth data, and dividing them into two groups, namely the model group and the Nimodipine group. Besides, taking 10 normal rats as a blank control group for comparison. The Nimodipine group will carry on the intervention in NIM.2 weeks later, carrying on the maze experiment again, comparing the tours of the rats in each group.3 weeks later, taking the brain of each group of rats to carry out the examination and comparison of brain organize NO and AchE.Main result and conclusion:(1) The data recorded before and after the labyrinth tour showed that t=2.967, which is a significant difference (P<0.01), indicating the AD rats model is successfully organized. Comparing the labyrinth tour data of medicine intervention group, the blank control group and the NIM group, the difference is obvious, for example, the sixth day of F=86.78, proved that NIM can improve memory function and can the AD restoration.(2) Comparing target NO of the three groups, F=79.302, (P<0.01), the difference has statistics significance. Further using LSD-t method to carry on 2 to 2 comparisons, we found the blank control group and the model group gives t=2.864, while the Nimodipine group and the model group gives t=2.936, and the Nimodipine group and the blank control group gives t=2.875, the result all show P<0.01, the difference has statistics significance. Therefore, we conclude that NIM treatment is related to the decreases of the brain AchE.(3) comparing ACHE of the three groups, F=37.56, P<0.01, the difference has statistics significance. Further uses LSD-t method to carry on 2 to 2 comparisons, the blank control group and the model group gives t=2.864, the Nimodipine group and the model group gives t=2.936, the Nimodipine group and the blank control group gives t=2.875, the result is all P<0.01, the difference has statistics significance. So we conclude that the NIM treatment is related to the decrease of the brain organize AchE.In summary, we extrapolated that NIM has therapeutic action on AD, and this action, just like the topic experimental result prompts, is related with:(1) reducing density of Ca2+in the cell.(2) reducing the brain organize NO density to decrease the free radical production, and promote free radical elimination.(3) reducing brain organize AchE density to improve the AD symptom.