| Objective:To investgate the changes of the ability of learning and memory and the vascular system in AD rats after establishing an AD model in wistar rats. And to investgate the pharmacodynamic effects and mechanisms of vascular protection of B-asarone on AD rats, so as to provide a new approach for prevention and treatment of AD.Methods:The rat model of AD was established by injecting both D-galactose and aluminum chloride into abdominal cavity. Their learning and memory were tested with Morris maze; Regional cerebral blood flow (rCBF) changes of right parietal lobe were measured with laser Doppler(LDP); Hemorrheologic changes were tesed by hemorheological analyser; The four reference indicators of the serum lipid were measured by full automatic biochemical analyser. The contents of lactic acid, pyruvic acid, and the activity of Na-K-ATP of cortex were measured by colorimetry. mRNA expression of ET-1,eNOS and APP was measured with real-time RT-PCR method; All the data was analyzed by SPSS 15.0.Results:1.The spatial navigation task latencies, the times through platform zone and the time for the first through platform zone in the target quadrant in probe task, rCBF and blood cell concentration of right parietal lobe, whole blood viscosity and plasma viscosity, hematocrit, erythrocyte electrophoretic time, fibrinogen,the levels of triglyceride, low density lipoprotein, high density lipoprotein, the contents of lactic acid, pyruvic acid, and the activity of Na-K-ATP of cortex, and ET-1 and eNOS mRNA expression in hippocampus of model control group rats were different from those of blank control group, P<0.05; The level of APP mRNA expression in model control group rats was higher than that in blank control group, though there was not a statistical difference, P>0.05;2. Compared with nimodipine group, (?)-asarone high does group, (?)-asarone middle does group and (?)-asarone low does group rats spatial navigation task latencies were shorter, P<0.05; Compared with Acorus tatarinowii schott group, (?)-asarone high does group,β-asarone middle does group and B-asarone low does group rats spatial navigation task latencies were not shorter, P>0.05;3. Compared with model control group, (?)-asarone high does group rats spatial navigation task latencies were shorter, in probe task the times through platform zone in the target quadrant were bigger, rCBF and blood cell concentration of right parietal lobe were higher, whole blood viscosity and plasma viscosity, hematocrit and fibrinogen were lower, erythrocyte electrophoretic time was shorter, the levels of total cholesterol and low density lipoprotein were lower, the contents of pyruvic acid was lower, the activity of Na-K-ATP was higher, and ET-1 mRNA expression in hippocampus was lower, P<0.05; The level of eNOS and APP mRNA expression in high does group rats was lower than that in model control group, though there was not a statistical difference, P>0.05; There was not a statistical difference in the level of low density lipoprotein of AD rats between high does group and blank control group, P>0.05;4. Compared with model control group, (?)-asarone middle does group rats spatial navigation task latencies were shorter, whole blood viscosity, hematocrit and fibrinogen were lower, erythrocyte electrophoretic time was shorter, the levels of total cholesterol and low density lipoprotein were lower, and the contents of pyruvic acid was lower, P<0.05; There was a statistical difference in the level of low density lipoprotein of AD rats between acorus tatarinowii schott group and blank control group, P<0.05;5. Compared with model control group,(?)-asarone low does group rats spatial navigation task latencies were shorter, whole blood viscosity, hematocrit and fibrinogen were lower, erythrocyte electrophoretic time was shorter, the levels of low density lipoprotein were lower, the contents of pyruvic acid was lower, P<0.05;.6. Compared with model control group, nimodipine group rats whole blood viscosity, hematocrit and fibrinogen were lower, erythrocyte electrophoretic time was shorter, the contents of pyruvic acid was lower, P<0.05;7. Compared with model control group, Acorus tatarinowii schott group rats whole blood viscosity and plasma viscosity, hematocrit and fibrinogen were lower, erythrocyte electrophoretic time was shorter, the levels of triglyceride and low density lipoprotein were lower, P<0.05; There was a statistical difference in the level of low density lipoprotein of AD rats between acorus tatarinowii schott group and blank control group, P<0.05; Conclusions:1. The rat model of AD established by injecting both D-galactose and aluminum chloride into abdominal cavity maybe have lower learning and memory, several vascular risks, cerebral metabolism dysfunction and higher ET-1 and eNOS mRNA expression in hippocampus, which might be a useful model for studies on the therapeutic effects and mechanisms of vascular protection of drugs for AD.2. High does of (?)-asarone could enhance AD rats' learning and memory; Middle and low does of B-asarone could enhance AD rats' learning;3. High does of (?)-asarone could enhance AD rats' rCBF and blood cell concentration of right parietal lobe;4. Low, middle and high does of (?)-asarone, nimodipine and Acorus tatarinowii schott could improve AD rats' hemorrheology, and high does of (?)-asarone is best among them;5. Low, middle and high does of (?)-asarone could decrease the levels of total cholesterol and low density lipoprotein, and high does of (?)-asarone is best among them; Acorus tatarinowii schott could decrease the levels of triglyceride and low density lipoprotein; and high does of B-asarone decrease the levels of low density lipoprotein better than Acorus tatarinowii schott;6. Low, middle and high does of (?)-asarone and nimodipine could improve AD rats' cerebral metabolism, and high does of B-asarone is best among them;7. (?)-asarone could dissipate phlegm for resuscitation and grow in intelligence and treat AD;8. High does of (?)-asarone could downregulate ET-1 mRNA expression in hippocampus of AD Rats, and maybe downregulate eNOS and APP mRNA expression, which elucidate the mechanisms of vascular protection of (?)-asarone on AD rats. |
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