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The Effect of Dlbutyphthalide on Expression of Nogo-A and IGF-1 Flowing Chronic Cerebral Hypoperfusion in Rats

Author: HuWenTao
Tutor: LuHong
School: Zhengzhou University
Course: Neurology
Keywords: Chronic cerebral ischemia Butylphthalide IGF-1 Nogo-A Learning and memory
CLC: R743.3
Type: Master's thesis
Year: 2009
Downloads: 31
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Abstract

Cerebrovascular disease is one of the world's most common age-related diseases, the incidence, morbidity and high recurrence rate, constitute the three major causes of death of the human heart disease, cancer, ischemic cerebrovascular disease accounted for all most of the cerebrovascular disease is the most common type of stroke. Chronic cerebral insufficiency was first proposed in 1990 by the Japanese physician to refer to all causes wide range of chronic insufficiency brain, causing brain ischemia and hypoxia, a series of brain dysfunction clinical manifestations diseases. Cerebrovascular disease plasticity of brain function has become the hot spot of the medical profession. Recovery of function following factors affect cerebrovascular disease is very complex, can be divided into incentives and disincentives two. After cerebral ischemia can lead to neuronal injury or death, while the internal mechanism of neuroprotection is also activated, the balance between the two determines the outcome of ischemic neuronal cells. The insulin-like growth factor (IGF-1) is recognized as a potential neuroprotective effect on cerebral ischemia, cerebral ischemia model in rats and sheep has been confirmed. It is a small molecule A polypeptide (7.5Kda), proinsulin-like structure, belong to the family of growth factor for mature neurons proliferation, differentiation, survival has an important role. . Studies have found that IGF-1 can improve the survival rate of neurons, can promote the formation of synapses, with the maintenance of nerve cell function, improving the role of learning and memory in aging animals. In hypertensive rats produced a spontaneous tendency to stroke cerebral ischemia-reperfusion model, exogenous injection of IGF-1 can make the rat hippocampal neurons apoptosis cells decreased neuroprotective effect on neurons after injury. Exist to limit the adult mammalian central nervous system after nerve injury nerve regeneration function of the protein, myelin-associated protein neurite growth inhibitory molecule Nogo is one of the most important protein, Nogo-A, Nogo-B, Nogo-C is divided into three kinds of major isomer, which is most closely related to the Nogo-A nerve regeneration, nerve regeneration in the mammalian central nervous system injury disorder is one important reason. Nogo-A elimination can lead to brain ischemia injury site structure remodeling and functional recovery. Nogo-A gene inactivation can be the same mice after stroke have a strong protective effect. Studies have shown that chronic cerebral ischemia impaired cognitive, due to the strong expression of Nogo-A, it can make damage to the fiber connections between neurons, inhibit the growth of the axons of newborn granule cells, inhibition of chronic cerebral missing blood neurological function and cognitive recovery. Butylphthalide (dl-butylphthalide NBP) is independently developed in China with independent intellectual property chemical drugs, security single integrated structure, a new drug to treat acute cerebral ischemia, chronic cerebral ischemia study compared less. This paper 2VO chronic cerebral ischemia models, evaluated by Morris water maze behavior in rats histological changes observed in rats with chronic cerebral ischemia process of adaptation in Nogo-A and IGF-1 expression by immunohistochemical methods, and to explore Butylphthalide its expression and experimental chronic brain ischemia. Materials and Methods Animal grouping and method of administration healthy Wistar rats 80, were randomly divided into Group A: control group (sham surgery solvent); B Group: ischemia group surgery solvent); C Group: ischemic low-dose treatment group (surgery the low dose NBP solvent); Group D: ischemic high dose treatment group (the surgical high dose NBP solvent); latter two groups in modeling the end of the water maze in February after the start of treatment, respectively 60mg/kg, 120mg/kg give Butylphthalide gavage, Butylphthalide diluted with peanut oil to 2ml. The first two groups were given daily peanut oil 2ml orally, are continuously fed daily for a month. 2 model was made blunt separation of B, C, D rats bilateral carotid artery ligation of the proximal end and the distal end of the line O of surgery; separation control group bilateral common carotid artery, but without ligation. After rats were reared under normal conditions. 3 the specimens produced after March, all rats perfused, decapitated brain, do paraffin sections with 4% paraformaldehyde for HE staining and immunohistochemistry. 4 OUTCOME MEASURES 4.1 in each group after 2VO March Morris water maze test and evaluation of learning and memory. 4.2 HE staining of rat hippocampus and temporal cortex neurons change. 4.3 immunohistochemistry of rat hippocampus and temporal cortex of IGF-1 and Nogo-A expression. (5) Statistical Methods All data are mean ± standard deviation (?) ± s application SPSS10.0 statistical software for data processing, among groups using single-factor analysis of variance (One-way ANOVA) with LSD method pairwise comparison, take a = 0.05 as the significance test standard. 1 experimental animal behavior observed after rats showed reduced food and water, poor spirit, abnormal behavior. 1-2 days after the rest of the group behavior, in addition to the recovery of the spirit of the group A resume is not obvious. 4-6 days B, C, D rats gradually returned to normal week. Cognitive ability was measured using the Morris water maze found after 2VO the March group B with group A was significantly longer escape latency time, across the platform significantly reduced the number, the differences were statistically significant (P <0.05): , D group and B group escape latency time was significantly reduced across the platform significantly increased the number, the differences were statistically significant (P <0.05), D and C groups to avoid the latency time is reduced across the platform frequency has increased The difference was statistically significant (P <0.05) HE staining Group A: hippocampal neurons did not show degeneration, necrosis, cell morphology is normal. Group B: a large number of neurons in the hippocampus of ischemic degeneration, necrosis, the normal number of nerve cells than group A was significantly reduced. Group C: hippocampal neuronal degeneration and necrosis than in group B to reduce the number of normal nerve cells than in group B increased significantly. Group D: hippocampal neuron degeneration, necrosis compared with group C was significantly reduced, the normal number of nerve cells was significantly increased compared with C group. 4.IGF-1 immunohistochemical staining in each group temporal cortex and hippocampus were observed, statistics and IGF-1 protein expression in positive cells, IGF-1 positive cells in the cortex, hippocampus and striatum with a wide range sexual expression, positive cytoplasm of neurons brownish yellow coloring. A group of IGF-1 protein was a small amount of expression of the B group IGF-1 expression and group A compared, the difference was not statistically significant (P> 0.05). Group C and Group D IGF-1 expression was significantly more than group B, the difference was statistically significant (P <0.05), and Group D IGF-1 expression was significantly more than the C group, the difference was statistically significant (P <0.05). 5.Nogo-A immunohistochemical staining in each group temporal cortex and hippocampus were observed, and statistics the number of positive cells Nogo-A protein expression of Nogo-A protein is mainly distributed in the rat brain small oligodendrocyte neurons and fibers cytoplasm and protrusions within, brownish yellow or brown coloring. Group A was Nogo-A expression, B group Nogo-A expression was significantly more than the A group, the difference was statistically significant (P <0.05), C group and D group Nogo-A expression was significantly less than in group B, the difference statistically significant (P <0.05), and Group D Nogo-A expression was significantly less than in group C, the difference was statistically significant (P <0.05). Conclusion after chronic cerebral ischemia after 3 months, IGF-1 expression was no significant change in the expression of Nogo-A increased significantly. 2. Butyl phthalide high dose and low-dose group may make chronic cerebral ischemia rat temporal cortex and hippocampus IGF-1 expression is increased, decreased expression of Nogo-A, the more obvious the role of high-dose group.

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