| Objective:To observe the effect of strengthening effect of small complex prescription of Chinese medicine in senescence accelerated mice(SAMP8) behavior, brain micro vascular pathological changes and hypoxia inducible factor-1a(HIF-1a) and vascular endothelial growth factor(VEGF) and telomerase(telomerase associated protein expression to discuss by improving the brain micro vascular pathologic morphology to improve animal action mechanism of learning and memory ability of small complex prescription of traditional Chinese medicine.Method:SAMP8 mice were randomly divided into four groups, including model group,memantine(memantine 2.6mg crude drug / kg body weight), traditional Chinese medicine high dose group(Fuzheng Quxie prescription(Radix ginseng, Rhizoma Chuanxiong,Rhizoma Coptidis), 13 g crude drug / kg body weight), small dose of Chinese medicine group(Fuzheng Quxie prescription and 2.6g crude drug / kg body weight), the other of the same genetic background of normal aging mice(senescence accelerated mouseresistance samr1) in mice to normal group, with 10 rats in each group, intragastric administration,daily 1 times, continuous administration for 12 weeks. By Morris water maze, avoid dark test and step-down test behavior observed in mice with learning and memory, and cognitive function; he staining to observe the changes of pathology in brain tissue of mice;immunohistochemical observation of protein expression in cerebral cortex of mice with vascular endothelial growth factor(VEGF) and telomerase; Western blot was used to detect the mouse brain tissue of HIF-1a, VEGF and telomerase expression.Results:1.Behavior test results show that the water maze test, compared with the normal group,model group in the platform quadrant swimming time and total time ratio, platform quadrant swimming distance and total distance ratio were significantly reduced(P<0.01).Compared with the model group, memantine group platform quadrant swimming distance and the total distance ratio(P<0.05) increased significantly. Compared with model group,the swimming time and total time in the platform quadrant of the large dose group of traditional Chinese medicine were significantly increased(P < 0.05, P < 0.01). The experiment results showed that, compared with the normal group, the latent period of model group was significantly shorter(P<0.01), and the error times were significantly reduced(P < 0.05). Compared with the model group, memantine group and Chinese medicine high dose group, the latency significantly prolonged(P < 0.05, P < 0.01),memantine group and Chinese medicine high dose and low dose group error number significantly reduced(P < 0.05). The step-down test, step-down test results show that compared with the normal group, model group, the latency of no significant change(P>0.05), but showed a tendency to reduce; and model group compared to traditional Chinese medicine high dose group, the latency of significant growth(P<0.01). Compared with the normal group, the error times of model group were significantly increased(P > 0.05).Compared with the model group, memantine group and traditional Chinese medicine in large and small dosage groups were significantly decreased the number of errors(P<0.05,P<0.01).2.Pathological observation, normal mice cortex micro vascular wall smooth and complete, clear structure, micro blood vessels around the gap small; model group mice cortex vascular wall thickness a, vascular lumen distortion, perivascular tissue gap increases obviously, reduction in the number of capillaries; to drug after mice cortex microvascular wall is complete, perivascular space compared with the model group reduced,capillary number compared with the model group increased.Pathological morphology of the neurons, Nissl staining showed that, normal group in CA1 area of hippocampus of mice cells arranged in neat rows and number of neurons,within the cytoplasm of a cell and the number of Nissl bodies more, cytoplasm was stained dark blue, pale blue nuclear; model group mice significantly reduced the number of neurons in hippocampal CA1 region, the more chaotic arrangement, the mirror display of Nissl body boundary is not clear or fuzzy, some nuclear pyknosis and dissolved, nuclear stained dark blue; Nissl bodies to after the administration of hippocampal CA1 neurons arranged more homogeneous and the number of neurons appeared different degrees of increase, in the cytoplasm of the more visible, karyopyknosis eased.3.Western-blot results showed that The expression of VEGF protein in the administration group was higher, but there was no significant difference between the model group and the model group.(P>0.05) compared with the normal group, model group, the expression of HIF-1a protein in brain tissue was significantly increased(P < 0.05).Compared with the model group, the expression of HIF-1a protein in the Chinese medicine group and memantine significantly decreased(P < 0.05, P < 0.01). There was no significant difference in the expression of Telomerase protein in each group(P>0.05)4.Immunohistochemical results showed that,compared with the normal group, the positive cell count of VEGF positive cells in model group was significantly decreased(P<0.01). Compared with model group, the positive cell count of VEGF positive cells was significantly increased(P < 0.05) inmemantinegroupand Chinese traditional medicine group. Compared with the normal group, there was no significant change of Telomerase positive count in model group(P> 0.05). Compared with the model group, after taking the drug, there was no significant change in Telomerase positive count(P>0.05).Conclusion:Fuzheng Quxie prescription can improve the memory of SAMP8 mice and cognitive ability,through improving cerebral angiogenesis related protein expression, increase the number of cerebral microvessels, protect neurons, ad slowed progress. Fuzhengquxie Decoction onAD may be related to improving the memory of mice, increase angiogenesis, protect neurons and other relevant. |
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