Research On The Tongmai Yizhi Granule In Treating Vaseular Dementia

Objective：To study the effect of Tongmai Yizhi granule on the cognitive function of Vascular dementia rats, and the pharmacodynamic effects of Tongmai Yizhi granule from several aspects:anti-inflammation,analgesic,anticoagulation,and improving cognition. The object of these experiments was to find that how Tongmai Yizhi granule treats vascular dementia,and provide the basis for further research and development.Method:Theoretical research:Collecting and analysing about the literature data of dementia.To explore the essence of that phlegm and blood stasis obstructed in orifice due to deficiency of the kidney and brain.Further illustrating the theoretical basis of Tongmai Yizhi granule treating vascular dementia.Experimental study:(1)to observe the therapeutic effects of Tongmai Yizhi granule on vascular dementia model rats.The bilateral carotid artery-ligated rats were used as the animal models.The common carotid arteries of sham group were just separated.The rats were randomly divided into6groups:sham group, model group,positive group,low dose groupg,middle dose groug, high dose group.Each group was administered during31days after the model of vascular dementia.We used Y electric maze to test the function of learning and memory in the second and fourth week.In the32nd day,hippocampal tissues were collected to do pathological analysis by microscope.We tested the activities of SOD and the content of MDA in blood serum and homogenate.(2)The mouse ear swelling caused by xylene and celiac capillary permeability increase induced with acetic acid in mice were method to study the anti-inflammatory effects.(3)hot plate and acetic acid twisting were method to study analgesic action.(4)The methods of grass,and cutting tail were used to detect the bleeding time and coagulation time.The effects of Rongban Tongmai granules on platelet aggregation in rabbits were observed using Born’s method.(5)Mice fed by the maximum concentration, maximum volume of Tongmai Yizhi granule, determined the largest doseamount per day. To observe the toxicity reaction of mice for two weeks, and further evaluate the safety of it.Result:(1) The experimental results of Tongmai Yizhi granule treating vascular dementia model rats showed that:Compared with sham group, incubation period (the time of running to safe zone)of model rats was significantly prolonged, and accuracy of learning and memory was decreased (P<0.01).In the serum and hippocampus of model rats,the activity of SOD was decreased, the content of MDA was increased (P<0.01).Each dose group of Tongmai Yizhi granule can obviously shorten the incubation period of VD rats in electric maze test (P<0.05,P<0.01).In serum and hippocampus,the activity of SOD was increased significantly(P<0.01),and the content of MDA was decreased obviously(P<0.01).Results of Morphology test showed:Hippocampal neuronal cells of model group were arranged disorderly, and cone cells were decreased significantly,The degree of cell swelling and vacuoles degeneration in each dose group of Tongmai Yizhi granule was lighter than the model group.The number of normal cone cells was more than the model group,and the arrangement was regularer than it.The experimental results of the general general pharmacodynamics and toxicology of Tongmai Yizhi granule showed that:(2)High dose group of Tongmai Yizhi granule can significantly inhibited the capillary permeability induced by acetic acid (P<0.05).The large, medium dosage significantly reduce the degree of mice ear swelling caused by xylene (P<0.05,P<0.01).(3)The large, medium dosage of Tongmai Yizhi granule increased pain threshold of mice (P<0.05, P<0.01),and reduced number of writhes induced by acetic acid in mice (P<0.05).(4)The bleeding time and coagulation time were more longer in the groups of large and middle dosages of Tongmai Yizhi granule than in the control group(P<0.05, P<0.01).Tongmai Yizhi granule could reduce the platelet aggregation rates induced by ADP.(5)Mice stomach were irrigated with the maximum concentration (4gcrude drugs·kg-1) and the maximum volume drug(0.03ml·g-1), and were observed for two weeks, Activities and diet of mice were normal,the growth of the weight was normal,too.On14th day,viscera which was dissected had no pathologic change using eys to see.Conclusion:(1)Tongmai Yizhi granule can improve learning and memory function of VD rats.The function mechanism of the treating vascular dementia may be related to it can improve the activity of SOD and reduce the content of MDA.It can effectively remove free radicals,and reduce the damage rate of the hippocampal pyramidal cells.Tongmai Yizhi granule can protect brain neurons in order to reduce the pathological damage of cerebral ischemia.(2)Tongmai Yizhi granule has certain anti-inflammatory and analgesic effects.it also can inhabit platelet aggregation in rabbits,and has the effects of ant-icoagulation.Maximum tolerance dose of Tongmai Yizhi granule was120gcrude drugs·kg-1·d-1,which was equal to150times of that for adults. It is safe to use in Clinical recommended dose.