| Objective:(1) Establishment of chronic cerebral ischemia animal model of cognitive impairment rats, to observe the effect of Bushen Huoxue medicine Shouwu yizhi capsule improved the learning and memory function.(2) To observe the effect of expression of Shouwu Yizhi Capsule on hippocampal tissue of rats with VEGF, Shh, Ang-1, Tie-2, Notch4 mRNA gene, to investigate the mechanism of signal regulation of shouwuyizhi capsule promoting angiogenesis.(3) To observe the effect of expression of Shouwu Yizhi Capsule on hippocampal tissue of rats with Hes3 and Stat3, Notch1 mRNA gene, to investigate the mechanism of signal regulation Shouwu Yizhi capsules on neuroprotection.Methods:To establish the model of chronic cerebral ischemia cognitive disorder of rats by permanent bilateral common carotid artery ligation, randomly divided into shouwuyizhi capsule group, nimodipine group, model group, sham operation group, 20 rats in each group. Shouwu yizhi capsule group rats were given Shouwu Yizhi Capsule(1 ml/100 g), nimodipine group were given Nimodipine Tablets(1 ml/100 g), saline model group and sham operation group were given intragastric administration, a total of 28 d. The ability of learning and memory in Morris water maze test in rats hippocampus; observation of vascular endothelial cells and neuronal ultrastructure under electron microscope; detecting the gene expression of hippocampal VEGF, Shh, Ang-1, Tie-2, Notch4 mRNA and Hes3, Stat3, Notch1 mRNA, real time quantitative PCR method.Results:1.(1) effects of Shouwu Yizhi Capsule on the learning and memory ability of VCI model rats: water maze results show that, place navigation and spatial Shouwu yizhi capsule group rats to explore experimental test score was significantly better than the model group and nimodipine group(P <0.01).(2) effects of Shouwu Yizhi capsules on cerebral ischemia in the hippocampus tissue surrounding the microvessel density: model group, nimodipine group, Shouwu yizhi capsule group compared with the sham operation group were increasing; each group compared with the sham operation group, there was significant difference(p<0.05, P, <0.01); compared with the model group, nimodipine group, Radix Polygoni Multiflori yizhi capsule group were significantly different(p<0.05, P, <0.01); compared with nimodipine group, the difference of shouwuyizhi capsule group was not significant(p>0.05).(3) effects of Shouwu Yizhi capsules on VCI model rat brain vascular endothelial cell ultrastructure of hippocampus: model group, microvascular endothelial cell cytoplasm and around the capillary height edema, mitochondria number in vascular endothelial cells decreased, most cristae and mitochondrial fusion disappear, part of the nuclear membrane fusion disappear. Shouwu yizhi capsule group and nimodipine group under light microscope showed: compared with the model group were obviously improved, the capillaries surrounding edema was lighter than in the model group, the basement membrane is basic and normal, vascular endothelial cells can be seen more mitochondria, is close to a normal state. In order to shouwuyizhi Capsule on endothelial edema group improved the most significant.(4) effects of Shouwu Yizhi capsules on rat hippocampal VCI model of VEGF, Shh, Ang-1, Tie-2, Notch4mRNA: compared with the sham operation group, model group, nimodipine group and shouwuyizhi capsule group of rat hippocampal VEGF, Shh, Ang-1, Tie-2, Notch4 mRNA expression was significantly increased(P< 0.05 ~ 0.01). Compared with the model group, nimodipine group and shouwuyizhi capsule group of rat hippocampal VEGF, Shh, Ang-1, Tie-2, Notch4 mRNA expression was significantly increased(P<0.05 ~ 0.01). Compared with nimodipine group, Shouwu yizhi capsule group of rat hippocampal VEGF, Shh, Ang-1, Tie-2, Notch4 mRNA expression was significantly increased(P<0.05 ~ 0.01).2.(1) neurons in hippocampal CA1 area of each cell structure group rats were sham operation normal. Model of rat hippocampal CA1 neurons rats nuclear membrane structure is not clear, chromatin mild condensation, mitochondria swelling, vacuolar degeneration, mitochondrial cristae, or even disappear, free ribosome reduced, cavitation region is formed in the cytoplasm, dissolved surrounding the fiber cell, the number of rough endoplasmic reticulum decreased, arranged in disorder, loose structure, fuzzy. Nimodipine group CA1 of rat hippocampus neural cells nuclear structure is clearly visible, Nissl bodies, mitochondria swelling, cristae part, endoplasmic reticulum expansion, also appeared degranulation. Shouwu yizhi capsule group CA1 of rat hippocampus neural cells of the nuclear membrane structure was clear, legible, double nuclear membrane, mitochondrion, microtubules and endoplasmic reticulum in the cytoplasm of abundant organelles and relatively clear, Nissl bodies lumpy or granular, relatively intact structure.(2) compared with the sham operation group, model group, the expression of nimodipine group and shouwuyizhi capsule group of rat hippocampal Notch1, Hes3 and Stat3 mRNA were significantly increased(P<0.01). Compared with the model group, the expression of nimodipine group and shouwuyizhi capsule group of rat hippocampal Notch1, Hes3 and Stat3 mRNA increased significantly(P<0.05 ~ 0.01). Compared with nimodipine group, the expression of shouwuyizhi capsule group of rat hippocampal Notch1, Hes3 and Stat3 mRNA were significantly increased(P<0.05).Conclusion:1 shouwuyizhi capsule has obvious improvement in memory, learning and cognition in cognitive impairment of chronic cerebral ischemia rats.2 Shouwu Yizhi Capsule by up regulating the expression of VEGF, Shh, Ang-1, Tie-2, Notch4 mRNA gene expression, promote angiogenesis.3 Shouwu yizhi capsule through up regulating expression of Notch1, Stat3, Hes3 gene, so as to reduce the damage of chronic hypoxia and ischemia of the nerve cell bodies of the neurons, the protection function and structural integrity, exerts a neuroprotective effect. |
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