| Objectives:Vascular dementia (VD), refers to the brain damage caused by cerebrovascular disease, has intelligence and brain functional lesion syndrome. According to statistics, the morbidity rate of dementia is about 5% in above 65-year-old people, the around 20% of which were VD. With the morbidity rate of cerebrovascular disease increasing recent year, the morbidity rate of VD was assumed tendency of ascensus. BushenHuoxuefang was active drug on treating VD, which were verificated by Clinical reseach. Explore the mechanism of BushenHuoxuefang treatment of dementia. The mechanism of BushenHuoxuefang's action in the treatment of VD was studied, from point of view of resisting oxidative damage, reducing inflammation cell factors, and adjusting blood current, by observation of BushenHuoxuefang's effect on praxiology of VD mice, pathomorphology of brain tissue, SOD, MDA, IL-1β, TNF-α, TXB2, 6-Keto-PGF1α and so on, so as to provide experimental basis for clinical treatment of VD.Methods:72 depuratory healthy male KunMing mice, the weights of 35-40g, offered by Hebei medical university experiment center, from which 12 mice were drown-off as sham operation group at random, were divided into four groups at random for the rest, that is, model group, BushenHuoxuefang high-dose group (called a high-dose group for short), BushenHuoxuefang low-dose group (called a low-dose group for short) and Nimodipine control group (called a control group for short), and each one takes 15 mice.According to the report, the model of VD was maken by ligating double arteria carotis communis and cerebral ischemia reperfusion. The sham- operation group mice only isolate bilateral common carotid artery, but not tail bloodletting, other groups by repeated blocking bilateral common carotid artery joint tail bloodletting 0.3mL.The second day after making the model, each mouse of treatment groups administered according to body weight. The dose of high-dose group is 14.28 g/kg of BushenHuoxuefang; the dose of low-dose group is 7.14 g/kg of BushenHuoxuefang; the dose of control group is 15.58 mg/kg of Nimodipine. The mice of sham operation group and control group were given 0.9%NaCl through watering stomach once a day, After making the model of VD, the number of surplus mice, removal of death .14 days after treatment, the first, mice Begin praxiology experiment by using water-labyrinth and jumping stand. Second, each group of mice took blood 3ml by buffo with Radioimmunoassay measured TXB2 and 6-Keto-PGF1α content. Third, the left side of the brain fixed with 4% formaldehyde, stained with HE and Thionine. Hippocampus brain tissue pathological changes were observed under light microscope. Fourth, the experiment used xanthine oxidase method to detect the SOD activity, used Thiobarbituric acid method to detect the content changes of MDA in cerebral tissue of VD mice. And last, IL-1β, TNF-αwere determined by methods of radio- immunoassay.The data were statisticed by using the SPSS for Windows 13.0 software processing, and the measurement data were expressed by modality of mean±standard deviation (±s). The single factor analysis of variance was adoptted when comparing among many groups, then"q"examination was adoptted when comparing with each other; the lever of significant difference was standarded as 0.05 and 0.01.Results:1 The effects of BushenHuoxuefang on praxiology of VD mice1.1 The effects of BushenHuoxuefang on learning record of VD mice in the experiment of water- labyrinth.Compared with the group of sham operation, the time of swimming of model group was prolonged, and the number of error of model group was increased, which was statistical difference (P<0.01). Compared with the model group, the time of swimming was shortened and the number of error was decreased in each treatment groups, which was statistical difference (P<0.05) or (P<0.01); Compared with the control group, there was statistical difference in learning record of the high-does group and low-does group (P<0.05); there was not statistical difference in learning record between the high-does group and low-does group (P>0.05).1.2 The effects of BushenHuoxuefang on memory record of VD mice in the experiment of water- labyrinth.Compared with the group of sham operation, the time of swimming of model group was prolonged, and the number of error of model group was increased, which was statistical difference (P<0.01); Compared with the model group, the time of swimming was shortened and number of error was decreased in each treatment groups, which was statistical difference (P<0.05 or P<0.01); there was statistical difference in memory record between the high-does group and control group (P<0.05); there was not statistical difference in learning record between the low-does group and control group (P>0.05); there was not statistical difference in learning record between the high-does group and low-does group (P>0.05).1.3 The effects of BushenHuoxuefang on learning record of VD mice in the experiment of jumping stand.Compared with the group of sham operation, the response period of model group was prolonged, and the number of error of model group was increased, which was statistical difference (P<0.01);Compared with the model group, the response period was shortened and the number of error was decreased in each treatment groups, which was statistical difference (P<0.05 or P<0.01); Compared with control group, there was statistical difference in learning record of the high-does group (P<0.05); there was statistical difference in learning record between the high-does group and low-does group (P<0.05); there was not statistical difference in learning record between the low-does group and control group (P>0.05). 1.4 The effects of BushenHuoxuefang on memory record of VD mice in the experiment of jumping stand.Compared with the group of sham operation, the latent period of model group was shortened, and the number of error of model group was increased, which was statistical difference (P<0.01); Compared with the model group, the latent period was shortened and the number of error was decreased in each treatment groups, which was statistical difference (P<0.05 or P<0.01); there was statistical difference in memory records between the high-does group and control group (P<0.05); there was statistical difference in memory records between the high-does group and low-does group (P>0.05); there was not statistical difference in memory record between the low-does group and control group (P>0.05).2 The effects of BushenHuoxuefang on Hippocampus pathomorphology of VD miceThe adumbration of hippocampal of sham operation group is clear, and the number of compact arrange pyramidal neuron in CA1 area is abundant, which's cell nucleus is large, and chromatospherite is clear, tigroid body in intracytoplasm is abundant. The pyramidal cell of model group in CA1 missed obviously, and which's order decreased, the rank is rarefaction, and the volume of nucleus, which structure was not clear, lessened, karyopycnosis, and some of which is triangle and polygon.The high-dose group of hippocampal CA1 area pyramidal cells only a very small depigmentation, a few become pyknotic nuclei, and nerve fibers are relatively regular arrangement. The low-dose group and control group mice hippocampal cerebral rehabilitation CA1 area pyramidal cells partial loss. The low-dose group was higher than the control group.3 The effects of BushenHuoxuefang on the content of TXB2 and 6-Keto-PGF1α in blood plasma of VD mice3.1 The effects of BushenHuoxuefang on the content of TXB2 in blood plasma of VD miceCompared with the group of sham operation, the content of TXB2 in blood plasma of model group was increased, which was statistical difference (P<0.01); After treatment, Compared with the model group, the content of TXB2 was decreased in each treatment groups, which was statistical difference (P<0.05 or P<0.01); Compared with the control group, the content of TXB2 of high-does group was decreased, there was statistical difference (P<0.05); there was not statistical difference in the content of TXB2 between the low-does group and control group (P>0.05).3.2 The effects of BushenHuoxuefang on the content of 6-Keto-PGF1α in blood plasma of VD miceCompared with the group of sham operation, the content of 6-Keto- PGF1α in blood plasma of model group was decreased, which was statistical difference (P<0.01); After treatment, Compared with the model group, the content of 6-Keto-PGF1α was increased in each treatment group, which was statistical difference (P<0.05 or P<0.01); Compared with the control group, the content of 6-Keto-PGF1α of high-does group was decreased, there was statistical difference (P<0.05); there was not statistical difference in the content of 6-Keto-PGF1α between the low-does group and control group (P>0.05).4 The effects of BushenHuoxuefang on the activity of SOD and the content of MDA in brain tissue of VD mice4.1 The effects of BushenHuoxuefang on the activity of SOD in brain tissue of VD miceCompared with the group of sham operation, the activity of SOD in brain tissue of model group was decreased, which was statistical difference (P<0.01); After treatment, Compared with the model group, the activity of SOD was increased in each treatment groups, which was statistical difference (P<0.01); Compared with the control group, the activity of SOD of high-does group was increased, there was statistical difference (P<0.05); there was not statistical difference in the activity of SOD between the low-does group and control group (P>0.05). 4.2 The effects of BushenHuoxuefang on the content of MDA in brain tissue of VD miceCompared with the group of sham operation, the content of MDA in brain tissue of model group was increased, which was statistical difference (P<0.01); After treatment, Compared with the model group, the content of MDA was decreased in each treatment groups, which was statistical difference (P<0.05 or P<0.01); Compared with the control group and low-does group, the content of MDA of high-does group was decreased, there was statistical difference (P<0.05); there was not statistical difference in the content of MDA between the low-does group and control group (P>0.05).5 The effects of BushenHuoxuefang on the content of IL-1βand TNF-αin brain tissue of VD mice5.1 The effects of BushenHuoxuefang on the content of IL-1βin brain tissue of VD miceCompared with the group of sham operation, the content of IL-1βin brain tissue of model group was increased, which was statistical difference (P<0.01); After treatment, Compared with the model group, the content of IL-1βwas decreased in each treatment group, which was statistical difference (P<0.01); Compared with the control group, the content of IL-1βof high-does group and low-does group was decreased, there was statistical difference (P<0.05 or P<0.01); there was not statistical difference in the content of IL-1βbetween the high-does group and low-does group (P>0.05).5.2 The effects of BushenHuoxuefang on the content of TNF-αin brain tissue of VD miceCompared with the group of sham operation, the content of TNF-αin brain tissue of model group was increased, which was statistical difference (P<0.01); After treatment, Compared with the model group, the content of TNF-αwas decreased in each treatment groups, which was statistical difference (P<0.05); Compared with the control group, the content of TNF-αof high-does group was decreased, there was statistical difference (P<0.05); there was not statistical difference between the control group and low-does group (P>0.05).Conclusions:The reseach showed that cerebral ischemia was the important reason of VD, and a lot of patho-factor participating the process of cerebral ischemia, such as abnormality of vasomotion, platelet aggregation, inflammatory factor, abnormality of free radical metabolism, and so on, which caused neurons impairment and induced the VD.The experiment proved that the BushenHuoxueFang could improve hippocamp pathomorphology and Learning and memory ability of VD mice, the mechanism of which was follow:1 BushenHuoxuefang could adjust TXB2/6-Keto-PGF1α balance, inhibit platelet aggregation, and improve hemodynamic and cerebral ischemia to improve the ability of learning and memory of VD mice.2 BushenHuoxuefang could regulate metabolism of free radicals and reduce oxidative damage of neurons by increasing SOD, decreased MDA, so as to improve the ability of learning and memory of VD mice.3 BushenHuoxuefang could significantly inhibit the release of inflam- matory cytokines, reduce the inflammatory injury of nerve cells by decreasing the content of IL-1βand TNF-αin brain tissue, so as to improve the ability of learning and memory VD mice...
|
PDF Full Text Request