Exploring Effective Mechanism Of Anti-dementia â…  On Rat Vascular Dementia

Vascular dementia (VD) is a kind of clinical symptom complex. It is caused by damaged brain tissue caused by ischemic, hemorrhagic, acute or chronic ischemic and hypoxia, and is characterized by disorder of senior cognition nerve function. The aggravation of VD has several steps. Early functional disturbance presents plaque-like distribulation and focal neural sings and symptoms, characterized by loss of functions of memory, calculation, apprehension, as well as disturbance of orient. In China, dementia incidence is 3.9 percent of people older than 65 and VD are 68.5 percent. VD are more popular than AD in the people older than 85 in British. In the united states, 10 percent people (from 85 to 88) will become dementia every year. At present more and more researchers pay their attention to VD, because VD can be prevented and have hopes to be cured in senior dementias. The drugs that can be used to cure VD are mainly cholinesterase inhibitor (ChEI), substances of improving cerebral circulation and cerebral metabolism.At present there are many hypothesizes to explain VD, cholinergic and free radical hypothesizes are more important, however. There are many researches about mechanism of VD and more and more evidences support that cholinergic system takes part in development of VD. There are damaged cholinergic and cognitive impairment in VD people, caused by change of cholinergic transmitters and receptors. Some researchers proposed that lipid peroxidation by free radical causes in tissue is an important reason of VD. Disbalance of free radical's metabolism in the progress of cerebral ischemia and reperfusion has a close relationship with disorder of learning and memory in VD.In order to get a better model of VD, we compared three VD model through analyzing behavior of rats respectively. The three models included models made by blocking and perfusing of double arteria carotis again and again in conjunction with intraperitoneal injection of nitroprusside(ischemia/reperfusion group, IRG), procerebrum ischemia model by blocking four blood vessels(four vessels blocking group, FVBG) and multi-infract dementia model(MID group, MIDG). Results: in water maze, rats'swimming velocity decreased significantly between 1st and 5th day in FVBG, hinted damaged limbs'movement and this might affect experiment's results. Latency and distance increased significantly between 2nd and 6th day in IRG and MIDG, however, a very large standard deviation in MIDG by different blocking areas and this might affect experiment's results. In step-down experiment, wrong times increased significantly on the 1st and 2nd day in FVBG and MIDG(P<0.05), and latency decreased significantly on the 2nd day(P<0.05), but wrong times of IRG increased significantly on the 1st and 2nd day(P<0.05 or P<0.01), latency decreased significantly on 2nd day(P<0.01). In step through test, wrong times increased significantly in FVBG and MIDG (P<0.05), latency decreased significantly (P<0.05) on the 2nd day, but IRG's wrong times increased significantly on the 2nd day(P<0.05) and latency decreased significantly (P<0.01). All of results showed IRG is better model.In order to explore mechanisms of Anti-dementiaâ… from aspects of cholinergic and free radical, we examined Ach contents, AChE activity, free radical and some correlated enzymes activity(MDA, SOD, Na+-K+-ATP enzyme, Ca²⁺-Mg²⁺-ATP enzyme, CAT and GSH-Px) in rats'brain of IRG, and detected BChE activity in blood plasm, in order to evaluated hepativ toxic ofAnti-dementaiaâ… .Show result:1. Anti-dementiaâ… 1.4mg,2.8mg/kg increased Ach contents(P<0.05) and decreased AchE activity in rat brain tissue(P<0.05).2. Anti-dementiaâ… 2.8mg/kg decreased MDA contents significantly in rat brain tissue(P<0.05).3. Anti-dementiaâ… 1.4mg/kg, 2.8mg/kg increased SOD and CAT activity significantly in rat brain tissue(P<0.05 and P<0.01), however, GSH-Px activity just had a tendency of increasing .4. Anti-dementiaâ… 1.4mg/kg, 2.8mg/kg increased Na+-K+-ATP enzyme activity significantly in rat brain tissue(P<0.05).5. Anti-dementiaâ… 1.4mg/kg, 2.8mg/kg didn't effects on BchE in blood plasm and suggested indirectly that Anti-dementiaâ… havn't Hepativ toxic obvious.Experiment results suggested that Anti-dementiaâ… ameliorate learning and memory function of VD rat through enhancing central cholinergic system, as well as reducing free radical damage, and brain tissue's energy metabolism, other mechanism of Anti- dementiaâ… reinforcing function of learning and memory need furth study.