[Effects of Shenwu capsule on learning-memory ability and cholinergic function of brain in AD-like rat model induced by chronic infusion of sodium azide by minipump].

Because of the proposed importance of mitochondrial cytochrome C oxidase (COX) decrease in Alzheimer's disease (AD) , the protective effect of Shenwu capsule on mitochondrial deficiency model rats and its pharmacological mechanism were investigated in present study. Rats were administered with azide at 1 mg . kg-1 . h-1 subcutaneously via an Alzet minipump for 30 days. Tweny-four hours after the operation, the rats were administered intragastrically by Shenwu capsule with the dose of 0. 45, 0. 9 and 1. 8 g . kg-1 . d-1 for one month. Then learning-memory ability was determined by the watermaze test and passive avoidance tests. The activity of choline-acetyl-transfertase(ChAT) and acetylcholinesterase (AChE) in hippocampus and cortex of rats were measured by radiochemical method and hydroxylamine colorimetry separately. M-cholinergic receptor binding ability (M-binding) was assayed by radio binding. Chronic infusion of sodium azide via minipump induced learning-memory deficiency of rats. Both ChAT activity and M-binding decreased in hippocampus and cortex of model rats, however, the activity of AChE increased in hippocampus and was not affected at the cortex. As the result, the cholinergic function of the brain decreased in model rats. Shenwu capsule significantly improved learning and memory ability and the mechanism may be related with the improved cholinergic function in model brain: ChAT activity and M-binding significantly increased in Shenwu treated groups compared with model group; and the increased activity of AChE in hippocampus returned to normal. Mitochondria, especially mitochondrial cytochrome C oxidase, may play the key role in the early event of AD. Chronic, partial in vivo inhibition of mitochondrial cytochrome C oxidase in rats provides a suitable model mimicking several aspects of AD. Shenwu capsule indicate effectiveness in AD-like mitochondrial deficiency model rats, so it would be applied in the treatment of AD.

Correlation of the cerebral microvascular blood flow with brain temperature and electro-acupuncture stimulation.

OBJECTIVE: To investigate the relationship between the temperature and the microvascular blood flow of the cerebral cortex, and the influence of electro-acupuncture (EA) on the cortical microcirculation. METHODS: High temperature spots on the anterior ectosylvian and low temperature spots on the posterior suprasylvian on the cortical surface of 20 cats were identified using cortical infrared thermography (CIT); the blood flow in the microcirculation on these spots was measured with laser-Doppler flowmetry. EA was given at Zusanli (ST 36) and changes in the blood flow in the cerebral cortex microcirculation were detected. RESULTS: 1) The mean temperatures on the high (34.83 +/- 0.24 degrees C) and low (32.28 +/- 0.27 degrees C) temperature spots were significantly different (P < 0.001); this was indicative of a temperature difference on the cortical surface; 2) The average blood flow in the microcirculation of the high (266.8 +/-19.2 PU) and low (140.8 +/- 9.9 PU) temperature spots was significantly different (P < 0.001). 3) On the cortical high temperature spots, the mean blood flow in the microcirculation significantly increased from 266.8 +/- 86.8 PU before EA, to 422.5 +/- 47.4 PU following 5 minutes of EA (58.35%; P < 0.01), and 431.8 +/- 52.8 PU 5 minutes after ceasing EA (61.84%; P < 0.01). 4) On the low temperature spots, there were no significant differences in blood flow following 5 minutes of EA (146.3 +/- 11.5 PU), and 5 minutes after ceasing EA (140.5 +/- 11.6 PU), when compared with that before acupuncture (140.8 +/- 9.9 PU; P > 0.9). CONCLUSION: The high temperature spots of the cortex are active functional regions of neurons with higher blood flow and a stronger response to EA. EA induces a significant increase in blood flow in the high temperature spots of the cortex.

[Effects of epimedium flavonoids on synapse related protein in brains of dementia transgenic mice].

OBJECTIVE: To investigate changes of synapse related protein, such as synaptophysin (SYP) and postsynaptic dense material 95 (PSD-95), in brains of 10 months old transgenic mice, and the effects of Epimedium flavonoids (EF) on expression of SYP and PSD-95 in brain of 10 months old of APP transgenic mice. METHODS: The mice of drug treated group were administered intragastrically by EF (at low doses of 0.03 and high dose of 0.1 g.kg(-1).d(-1)) from 4 to 10 months old. The mice of normal group and negative transgene group were administered of distilled water by the same way. The expression of SYP in CA1, CA3, and dentate gyrus (DG) areas of hippocampus and cortex, and PSD-95 in hippocampus and cortex were detected by immunohistochemistry and Western blot respectively. RESULTS: Compared to negative transgenic mice, the expression of SYP in cortex was decreased by 51.3% (P < 0.01). The IOD value of SYP immuno-reactivity cell in CA1, CA3 and DG areas of hippocampus in 10 months old transgenic mice were significantly decreased (the suppression rates were 59.1%, 57.7% and 56.5% in CA1, CA3 and DG respectively, all P < 0.01). The expression of PSD-95 in cortex decreased by 36.4% (P < 0.01). The count of PSD-95 immuno-reactivity cell in CA1 area of hippocampus decreased with the suppression rate of 18.5% (P < 0.05). After being administered intragastrically by EF for 6 months, the expression of SYP in cortex of EF low doses and high dose group mice increased by 40.0% (P < 0.05) and 106.4% (P < 0.01) respectively in comparison with that of the control group. The IOD value of SYP immuno-reactivity cell in hippocampal CA1, CA3 and DG areas of EF low and high dose group mice were all significantly increased (all P < 0.01). The expression of PSD-95 in cortex of EF low and high dose group mice increased by 57.3% (P < 0.05) and 84.3% (P < 0.01) respectively when compare to the control group. The count of PSD-95 immuno-reactivity cell in CA1 area of hippocampus of mice in EF high dose group increased by 22.5% (P < 0.05). CONCLUSION: Epimedium flavonoids could protect the synaptic structure and function by promoting the expression of synaptophysin and postsynaptic dense material 95, which suggest that Epimedium Flavonoids may have a promising application prospect in improving the synaptic impairment of AD.

[Evaluation of tongue manifestation of blood stasis syndrome and its relationship with blood rheological disorder in a rat model of transient brain ischemia].

OBJECTIVE: To study the tongue tissue blood oxygen saturation measurement for evaluating tongue manifestation of blood stasis syndrome, and to explore its correlation with blood rheological disorder in a rat model of acute transient brain ischemia. METHODS: Twenty-eight SD rats were randomly divided into sham-operated group and ischemia group. Middle cerebral artery occlusion was induced by thread in rats of the ischemia group. Tongue tissue blood oxygen saturation, neurological severity score and the changes of blood viscosity, red blood cell deformity, thrombin time and fibrinogen in the rats were measured after 24-hour reperfusion. RESULTS: Blood viscosity and the content of fibrinogen in the ischemia group were significantly higher than those in the sham-operated group. Red blood cell deformity, thrombin time and tongue tissue blood oxygen saturation in the ischemia group were decreased as compared with the sham-operated group. There was a positive correlation between red blood cell deformity and tongue tissue blood oxygen saturation. CONCLUSION: Tongue tissue blood oxygen saturation is a good measurement for evaluating blood stasis in a rat model of focal cerebral ischemia, and this model can be used as a rat model of stroke with blood stasis syndrome.

Learning-memory deficit with aging in APP transgenic mice of Alzheimer's disease and intervention by using tetrahydroxystilbene glucoside.

OBJECTIVE: To investigate learning-memory deficit in different ages of AD-like APP transgenic mice and to observe the protective effects of 2,3,5,4'-tetrahydroxystilbene-2-O-beta-D-glucoside (TSG), which is the main component of Polygonum multiflorum, on learning-memory abilities. METHODS: PDAPPV717I transgenic (Tg) mice were randomly divided into 3 model groups (4, 10 and 16 months old mice) and TSG treated (at doses 120 and 240 micromol/kg/d) groups. TSG was administered to some Tg mice with an age range 4-10 months. In untreated 10 months old Tg mice, the TSG was administrated to those falling in the age range 10-16 months. For the control group we adopted the same age and background C57BL/6J mice. The learning-memory ability was measured by applying Morris water maze (MWM) and object recognition test (ORT). RESULTS: In the 4 months old PDAPPV717I Tg mice, the learning-memory deficit was detected. The escape latency in MWM was prolonged, and the discrimination index decreased in ORT. In the 10 months old Tg mice, the learning-memory deficit was aggravated. TSG improved all spatial learning-memory impairment in MWM as well as the object recognition impairment in ORT. In the 16 months old Tg mice, the learning-memory deficit remained to exist but abated a lot. TSG showed significant improvement in learning-memory ability in both MWM and ORT. CONCLUSION: PDAPPV717I transgenic mice with an age range 4-16 months revealed the existence of learning-memory deficit compared with the control group. Tetrahydroxystilbene glucoside not only prevents, i.e. at an early stage, the learning-memory deficit in AD-like model, but also can reverse the learning-memory deficit in the late stage of AD-like model. Thus, TSG could be considered among the future therapeutic drugs indicated for the treatment of AD.

[Effect of shenwu capsule on the peripheral blood lymphocyte DNA of rat model induced by beta-amyloid injection].

OBJECTIVE: To investigate the effect of the new Traditional Chinese Compound Shenwu Capsule on the damage of lymphocyte DNA and lipid peroxidation in peripheral blood of rats induced by beta-amyloid injection. METHOD: The animal model was made by injection of beta-amyloid25-35 into hippocampus of rats. DNA damage of lymphocytes was measured by the single cell gel electrophoresis (SCGE) combined with the laser scanning confocal microscopy (LSCM). The content of malondialdehyde (MDA) was determined by TBA assay. RESULT: Shenwu Capsule decreased the rate of the comet-like cell, comet-like cell lengh (TCL), and tail moment (TM) of lymphocytes in peripheral blood of model rats. Shenwu Capsule also declined the MDA content in serum of Abeta model rats. CONCLUSION: Shenwu Capsule has protective effect on peripheral blood lymphocyte DNA.