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Experimental Study of Butylphthalide on Learning and Memory Disorder in Rats with Vascular Dementia

Author: WangXinDong
Tutor: ChenZuoZuo
School: Zhengzhou University
Course: Rehabilitation Medicine and Physical Therapy
Keywords: Vascular dementia Butylphthalide iNOS p38MAPK Apoptosis Hippocampus Tunel staining Immunohistochemistry
CLC: R965
Type: Master's thesis
Year: 2011
Downloads: 114
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Abstract

Background and purpose of vascular dementia caused by cerebrovascular disease refers to learning and memory deficit as the main clinical manifestations of chronic acquired severe cognitive dysfunction syndrome, cerebrovascular disease common sequelae. Apoptosis is currently considered the pathogenesis of vascular dementia is one. The hippocampus is associated with learning and memory function main brain function, easily ischemic injury. Studies suggest that chronic cerebral ischemia can cause apoptosis in the hippocampus, degeneration, atrophy, injury often causes learning and memory impairment appears, for vascular dementia pathology. iNOS is inducible nitric oxide synthase. p38MAPK p38MAPK signaling pathway is a key member. Most studies have found that, iNOS and p38MAPK in acute ischemic tissue by apoptosis involved in brain injury. Butylphthalide is independently developed by China National Class treatment of non-hemorrhagic stroke generation anti-ischemic drugs. It not only can reconstruct the path of blood supply to ischemic tissue area to protect against ischemic brain tissue, and mitochondria from giving protection, reducing calcium store release of calcium ions and other aspects of resistance to apoptosis, which play against cerebral ischemic injury role of the brain function to achieve recovery, to achieve the purpose of clinical symptoms. Although the role of apoptosis resist it, but this is a complex process of apoptosis, use it to learning and memory impairment in vascular dementia treatment will have an effect, and is currently reported. We intend to adopt vascular dementia rat model for the study area in the hippocampus, iNOS and p38MAPK expression, apoptosis and learning and memory ability of observed indicators to observe their changes after Butylphthalide intervention in order for the clinical treatment of vascular Dementia finding new drugs and to explore the specific vascular dementia molecular mechanisms. Materials and Methods 1. Experimental animals groups: the 42 adult male Wistar rats were randomly divided into sham operation group, model group, Butylphthalide groups. Two experimental animal model: carotid artery with a pair of permanent ligation method. Three groups of rats were anesthetized by intraperitoneal injection, after the success of the neck along the median longitudinal skin incision, blunt separated subcutaneous fascia and muscle tissue to bilateral common carotid arteries. Butylphthalide group with model group rats, each side of the carotid artery with a 0 silk for dual ligation surgery, from the middle cut, suture the incision. After warm, to be awake, clean the cage back into the box to continue feeding. In addition to sham rats do ligation, but also according to the surgical procedure to operate. 3 test dose, method and duration: 2 weeks after surgery, according to the treatment group Butylphthalide 65 mg / kg, given orally, model group and sham group subjected to the same process, but did not give drugs. Three groups were once a day for 2 months. 4 of learning and memory capacity determination: February after testing using Y-type maze learning and memory abilities of rats to electric shock in rats ran directly after the security zone for the correct responses to 10 consecutive appeared 9 times before the correct response on behalf of the required number of shocks learning ability in rats. After 24 hours, each rat test 10 times, 10 times the note appears in the number of correct responses to the number of correct responses on behalf of memory. 5 hippocampal tissue sections of the production: the maze test, the hippocampus has been drained of blood from the brain separated into to 4% formaldehyde and maintained within 24h, then conventional dehydration, transparent, dipping wax, embedding, coronal Direction slices (thickness 5μm) to spare. 6 immunohistochemistry and Tunel staining: iNOS and p38MAPK by immunohistochemistry and Tunel staining kit requirements and 400 optical microscope. 7 image acquisition and analysis: The German Lecia photomicrograph systems and Biosens Digital Imaging System v1.6 on each rat on each slice randomly selected area roughly the same measure three horizons, photographed and measured gray value, whichever is average as the result of the slice, then put all the slices and then averaged the results were as mean ± standard deviation (x ± s) expressed. 8 Data statistical tests: Using SPSS17.0 statistical software, single-factor analysis of variance between groups using LSD method, P lt; 0.05 considered statistically significant. Results 1. Three rats learning and memory situations: three groups of rats to sham-operated rats to learn the fastest, least forgotten. Learning, 10 consecutive correct responses appeared nine times before the advent of this result the least number of shocks required for 34.07 ± 3.09 times; 24 hours after leaving behind a correct response 8.07 ± 1.07 times. The group Butylphthalide slowly learn the required number of shocks required to 60.78 ± 4.26 times, forgetting more, left 6.42 ± 1.45 times. Model group, the slowest. Society requested number of shocks needed to 74.21 ± 3.0 times, 10 times in 24 hours, the number of correct responses legacy of 4.64 ± 1.49 times. Statistical comparison between the three groups were significantly different, P values ??were less than 0.05. 2. Hippocampal iNOS immunohistochemical staining: iNOS immunohistochemical staining in the cytoplasm should appear for different degrees of brown. In the sham group, the optical microscope to see only a very small amount of light brown cells; dark brown and yellow in the model group showed greater in number; Butylphthalide group saw was brown, fewer. Three groups of positive cells district average gray value, Butylphthalide group (72.51 ± 4.80) than the sham group (7.07 ± 2.33) than the model group: 72.51 ± 4.80. And the model with the sham group, P lt; 0.05. 3. Hippocampal p38MAPK immunohistochemical staining: p38MAPK staining in the nucleus, but the degree of staining due to the number and different p38MAPK content. In the sham group, the optical microscope to see only a small amount of light brown yellow cells; while in model group saw a lot of dark brown and yellow cells. In Butylphthalide group saw positive cells are brown, and the number is relatively small in terms of the model group, rather than the sham group and more. Three groups of positive cells district average gray value, Butylphthalide group (65.02 ± 4.14) than the sham group (10.20 ± 2.32) than the model group: 70.72 ± 4.81, and the model with the sham group P lt; 0.05 4. hippocampal apoptosis Tunel staining: in the sham group had a small amount of nuclei were stained brown cells exist, cytoplasmic concentration, cell body decreases, the spread of nuclear fragmentation. Such cells in the model group increased significantly. In Butylphthalide group, such cells also were seen, but the number is reduced compared with the model group than the sham group. Three groups in the number of apoptotic cells in the model group the most, followed by the number of Butylphthalide group, sham group appears in the smallest number. Respectively (61.92 ± 4.19)%; (35.00 ± 3.32)%; (5.07 ± 2.40)%, P lt; 0.05. Conclusions 1. Butylphthalide vascular dementia rats improved learning and memory impairment can play the role. 2.iNOS and p38MAPK and vascular dementia occurrence and development of learning and memory disorders there is a certain relationship. 3 Butylphthalide vascular dementia rats learning, memory improvement, possibly by reducing the expression of iNOS and p38MAPK, blocking apoptosis in the hippocampus results.

Experimental Study of Butylphthalide on Learning and Memory Disorder in Rats with Vascular Dementia

Abstract

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