Exploring Therapeutic Action And Mechanisms Of Anti-dementia Ⅰ On AD Rats

Alzheimer's disease is a degenerative disease in central nervous system mainly characterized by progressive decline of cognitive function and damaged memory. Along with increasing human's average life, AD has become one of the principal diseases that threaten quality of life in human's old age. Incidence of AD increases year by year and AD is also main part of dementias in old age. Because causes of AD has not been completely illuminated, there are not specific medicines to cure AD. Now the medicines used in clinic just can sustain cognitive function in short term, however , they can not block pathological progress of AD. These medicines are also expensive and can make patients who have to use them in long term suffer from increasing financial burden. So to explore specific and cheap medicine can protect patients'health and decrease patients'financial burden, this is of great benefit to patients and society.In this research, we explored therapeutic actions of anti-dementiaⅠon AD and primarily explored its mechanisms. This research was composed by three departments.The first, we studied therapeutic actions of anti-dementiaⅠin AD model rats induced by intraperitoneal injection of D-galactose in 7 weeks. Positive control group was given donepezil hydrochloride (1.75mg/kg), anti-dementiaⅠgroups was given anti-dementiaⅠ(0.7, 1.4, 2.8mg/kg) by intragastric administration. The procedure of giving medicine was administrated in consecutive 7 days and the following tests included Morris water maze and step-down test. When step-down test was over, we got rats'brain quickly. A half of brain was used to suffer examine of pathology, the other was used to make cerebrum tissue homogenate which would be used to examine MDA and SOD.Results: anti-dementiaⅠ(0.7,1.4,2.8mg/kg) groups showed latency decreased significantly (P<0.05), distance decreased significantly (P<0.05), start angle decreased significantly (P<0.05或P<0.01). 1.4, 2.8mg/kg groups showed change of probing was stepped up significantly from marginal form, stochastic pattern to tendency, linear type(P<0.05或P<0.01). 1.4, 2.8mg/kg groups showed wrong times decreased significantly in the 1st, 2nd day in step-down test (P<0.05). Pathological examine showed 1.4, 2.8mg/kg groups had a improved hippocampal and cortical damage induced by D-galactose. 1.4, 2.8mg/kg groups showed MDA decreased and SOD increased significantly(P<0.05).The second, we studied therapeutic actions of anti-dementiaⅠin AD model rats induced by Aβ25-35, which was injected into the hippocampus of rats. The time of giving medicine was 7 days. The following tests included Morris water maze and step-down test. When the tests were over, we observed hippocampal and cortical pathological change through pathological examine.Results: anti-dementiaⅠ(0.7, 1.4, 2.8mg/kg) groups showed latency decreased significantly(P<0.05或P<0.01), starting angle decreased significantly (P<0.05或P<0.01). 1.4, 2.8mg/kg groups showed distance decreased significantly (P<0.05). 0.7, 1.4, 2.8mg/kg groups showed change of probing was stepped up significantly from marginal form, stochastic pattern to tendency, linear type(P<0.05或P<0.01). In step-down test, 2.8mg/kg group showed wong times decreased significantly in the 1st, 2nd day (P<0.05), latency increased significantly in the 2nd day (P<0.05). Pathological examine showed 2.8mg/kg group had a improved hippocampal and cortical pathological damage induced by Aβ25-35.The third experiment was about mechanism of anti-dementiaⅠin AD model rats induced by Aβ25-35. We made AD model induced by Aβ25-35, which was injected into the hippocampus of rats.We observed neuronal appearance by light microscope, and examined SOD, CAT, MDA, GSH-PX, Na~+—K~+ ATP enzyme in cerebrum tissue homogenate. We also used flow cytometry and electron microscope to examine neuronal apoptosis. All of these were designed to explore the mechanism of anti-dementiaⅠon AD from the aspects of free radical and apoptosis.Results: 1.4, 2.8mg/kg groups showed MDA decreased significantly (P<0.05), SOD increased significantly (P<0.05), CAT increased significantly (P<0.05或P<0.01) in rats'cerebrum tissue, however, GSH-PX, Na~+—K~+ ATP enzyme didn't change significiantly (P>0.05). Electron microscope and flow cytometry didn't detect apoptosis in rats'cerebrum tissue.Conclusion: anti-dementiaⅠhas therapeutic action on AD rats and its mechanism might have relation with preventing from damage induced by free radical, however, its mechanism might not have relation with anti-apoptosis.