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The Mechanism Study of Buyanghuanwu Decoction on the Ability of Learning and Memory of Vascular Dementia Rats

Author: TangJingLong
Tutor: LiYuMing;GaoWeiJuan
School: Chengde Medical College
Course: Pathology and Pathophysiology
Keywords: BYHWD Vascular Dementia Hippocampal CA1 LTP ERK2 CaMKIIβ
CLC: R285.5
Type: Master's thesis
Year: 2010
Downloads: 133
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Abstract


Very sensitive to brain ischemia and hypoxia, which repeated cerebral ischemia-reperfusion injury and chronic hypoperfusion is the main reason to cause vascular dementia (Vascular Dementia, VD) and the importance of restricting the treatment of ischemic cerebrovascular disease efficacy factors, so as to explore the pathophysiological mechanisms of cerebral ischemia-reperfusion injury and to strengthen prevention research is necessary. Hippocampal CA1 region is considered to be an important part of the higher nervous activity of learning and memory, cerebral ischemia one of the most sensitive areas. During the development of ischemic cerebrovascular disease, extracellular signal-regulated kinase -2 (Extracellular signal-regulated kinase, ERK2) can regulate hippocampal neuron growth, development, differentiation, protect nerve cells; and ERK2 can hippocampus cell dendritic morphological changes in dendritic handle and dendritic spines protruding filopodia involved in neural element morphological plasticity. Calcium / calmodulin-dependent protein kinase II (calcium / Calmodulin-dependent protein kinase II, CaMK II) is an important target of Ca2 enzyme, the brain is the most abundant protein kinase, is highly expressed in the hippocampus and cerebral cortex sudden dense matter aftertouch (postsynaptic density, PSD), which catalyzes a variety of protein phosphorylation occurs, leading to changes in its downstream series of biochemical reactions; simultaneously both structural proteins, and studies suggest that CaMKII signal transduction pathway may be a receptor plasticity, learning, memory and other major part of the complex mechanisms; long-term potentiation (long-term potentiation, LTP) can objectively reflect synaptic plasticity; ischemia-reperfusion injury combined with learning and memory defects the VD pathophysiological process CaMKIIβ changes been reported. Yiqihuoxue Chinese BYHWD (Buyanghuanwu decoction, BYHWD) is the classic recipe of traditional Chinese medicine, commonly used drugs for the treatment of cerebral vascular disease, but the means by which the signal transduction pathway protect the brain tissue, improve learning and memory, and its mechanism is not yet fully elucidated . This subject by observing yang Huan Wu Tang the VD hippocampal CA1 region of nerve tissue ERK2 CaMKIIβ protein expression of the hippocampal CA1 region postsynaptic potential changes, explore Buyang five soup to improve the molecular mechanisms of learning and memory . Purpose of the first part BYHWD learn of vascular dementia rat behavior and hippocampal CA1 neuron morphology: observation Bu Yang Huan Wu Tang learned of vascular dementia rat behavior and hippocampal CA1 yuan morphological impact. Methods: adult male SD rats were randomly divided into sham group, model group, BYHWD group, nimodipine group. Prepared rat vascular dementia model using the four-vessel occlusion, Bu Yang Huan Wu Tang (50g/kg/d) and nimodipine (20mg/kg/d), intragastric administration continued for a month postoperative 30d water Labyrinth assay the rat behavioral change; HE staining was used to observe the morphological changes of the hippocampal CA1 region neurons and neuron counting. Results: Morris water maze test showed that, compared with the sham group, model group were significantly longer escape latency across the platform area had significantly fewer (P lt; 0.05). Compared with the model group, Yang Huan Wu Decoction group, the nimodipine group of rats escape latency was significantly shortened, the number of times through the platform area was significantly increased (P lt; 0.05). HE staining: model group appear obvious pathological changes in rat hippocampal neurons, hippocampal neurons arranged due to the rules, the boundary is not clear, normal cells disappear, the stain of the nucleus region appear coagulation necrosis cell depigmentation rats number of hippocampal CA1 neurons decreased significantly (P lt; 0.05); compared with the model group, BYHWD group, significant improvement in the nimodipine group of pathological changes in rat hippocampal neurons, neurons arranged in neat rows, even The structural integrity of the cell, close to the sham group, the number of hippocampal CA1 neurons was significantly increased (P lt; 0.05). Summary: BYHWD can improve learning and memory in rats with vascular dementia, reduce cerebral ischemia and reperfusion-induced neuronal damage. The second part BYHWD vascular dementia rat hippocampal CA1 region of brain tissue the LTP expression of the impact of purpose: To observe the Bu Yang Huan Wu Tang VD hippocampal CA1 region LTP. METHODS: The experiment grouping and modeling methods with the first part. Adopt-term potentiation in the rat hippocampal CA3-CA1 Divisional recording method to record the hippocampal CA1 region LTP value. Results: Compared with the sham group, model group rat hippocampal CA1 LTP expression significantly decreased (P lt; 0.05). BYHWD group compared with the model group, the the nimodipine group of rats hippocampal CA1 LTP expression was significantly increased (P lt; 0.05). Summary: BYHWD enhance LTP, improve learning and memory function. Third part BYHWD ERK2 protein expression of vascular dementia rat hippocampal CA1 region of brain tissue Objective: To observe BYHWD learning the memory related protein ERK2 expression VD rats. METHODS: The experiment grouping and modeling methods with the first part. Rat CA1 region of the hippocampus ERK2 protein expression changes observed using Western Blots method. Results: Compared with the sham group, ERK2 protein expression in hippocampal CA1 region was significantly lower (P lt; 0.05). Compared with the model group, BYHWD group, the the nimodipine group of rat hippocampal CA1 region ERK2 protein expression was significantly increased (P lt; 0.05). Summary: BYHWD can promote VD rats ERK2 protein expression, so as to protect hippocampal neurons, improve learning and memory function. The fourth part BYHWD VD rat hippocampal CA1 region the brain tissue CaMKIIβ protein Objective: To observe the BYHWD VD rats learning the memory related protein CaMKIIβ of expression. METHODS: The experiment grouping and modeling methods with the first part. Rat CA1 region of the hippocampus CaMKIIβ protein expression changes observed using Western Blotting method. Results: Compared with the sham group, model group rats hippocampal CA1 zone CaMKIIβ, protein expression was significantly lower (P lt; 0.05). Compared with the model group, BYHWD group, the the nimodipine group of rats the hippocampal CA1 the District CaMKIIβ protein expression was significantly increased (P lt; 0.05). Summary: BYHWD promote vascular of dementia rats CaMKIIβ protein expression, thus contributing to the synapse build, improve learning and memory function. Conclusion 1. BYHWD could improve learning and memory abilities of rats with vascular dementia, reduce cerebral ischemia and reperfusion-induced neuronal damage. 2. BYHWD enhance LTP expression of vascular dementia rats, thus improving learning and memory function. Buyang five soup can upregulate VD ERK2 protein expression in rat hippocampal CA1 region of brain tissue to promote neuronal damage repair, improve learning and memory function. 4. Promote BYHWD the VD rat hippocampal CA1 region of brain tissue CaMKIIβ protein expression, enhanced synaptic plasticity, thereby promoting synapse build and improvement in learning and memory function.

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