Protective Effects Of Dipfluzine On The Brain In Alzheimer's Disease Rats And Naturally Aged Rats

With the tendency of aging, senile dementia has become the focus in the medical field. The morbidity of senile dementia is increased remarkably with the growing age. Alzheimer's disease (AD), the most common of the senile dementia, has serious effect on both the work and life of people. But there is no effective drug for treating senile dementia at present. Dipfluzine (Dip), a novel calcium antagonist, was first synthesized by Hebei Medical University. It is lipophilic, which enables it to cross the blood-brain-barrier and achieve effective drug concentration in the cerebrospinal fluid. Dip could inhibit calcium influx and maintain intracellular calcium homeostasis. It could improve cerebral microcirculation and assure supply of energy and nutrition in cells. It could improve the amnesia induced by sodium nitrite and sodium pentobarbital in mice and protect the ischemic brain in rat by reducing the disturbance of cortical function and the imbalance between excitatory and inhibitory amino acids.The present study is undertaken to observe if Dip possesses the protective effects on the brain in naturally aged rats and AD rats induced by intraperitoneal injection with AlCl3 and explore its mechanisms. The concrete experiments are as follows:1. Protective effects of dipfluzine on the brain in AD ratsObjective: To study the protective effects of Dip on the brain in AD rats by measuring learning and memory ability, some biochemistry indexes in brain tissue and blood serum and expression of choline acetyltransferase (ChAT) in the brain.Methods: Healthy Male SD rats (350-400g) were randomly divided into 5 groups: (1) Control group; (2) Model group; (3) Nim group (5.0mg/kg, ig); (4) High dose Dip group (10.0mg/kg, ig); (5) Low dose Dip group (3.0mg/kg, ig). Rats in Control group were treated by intraperitoneal injection with saline 4ml/kg while the rats in the others were treated by intraperitoneal injection with 1.25%AlCl3 by the same volume for 60 days. The step-down avoidance test was used to observe the learning and memory ability of rats. Biochemisty method was used to determine SOD, T-AOC and MDA in brain tissue and blood serum. All the rats were killed by decapitation and the brains were removed and immersed in 4% pareformaldehyde, then the brains were processed and embedded in parafin. Coronal sections were taken from the dorsal hippocampal and stained with HE. The sections were examined with the light microscope and neuronal damage was observed. The expression of ChAT in neuron was observed by immunohistochemisty.Results: 1. The learning and memory ability of the rats in model group was significantly lower than that in control group. The reactive time and the time of stimulation of the rats in model group were significantly longer than that in control group, and the number of errors was more and the step down latency was significantly shorter as well. Both Nim and Dip 10.0mg/kg improved the spatial disorder of the model rats remarkably, while Dip 3.0mg/kg could improve some index only. 2. Compared with control group, the content of MDA in the brain tissue and blood serum was increased obviously and the activities of SOD and T-AOC were decreased clearly in model group. In the groups treated with Nim and Dip, the content of MDA was decreased while activities of SOD and T-AOC were increased in different degree. 3. Observation by light microscope: The hippocampal structure of rats in control group was normal as well as the morphology of pyramidal neurons and the number of the normal hippocampal cells in CA1 area was 180±10. In model group, the hippocampal structure was destroyed, and almost all pyramidal neurons were either shrinked or dissolved and the number of the normal hippocampal cells in CA1 area was lower(118±12) than that in control group. Nim and Dip 10.0mg/kg lightened the injury in different degree and decreased the number of dead neurons and the number of the normal hippocampal cells in CA1 area was 154±14 and 159±14. Dip 3.0mg/kg could improve the damage of brain...