| Background and objectiveWith the aging population of the world, chronic cerebral hypoperfusion has already been an important clinical difficult problem to threaten mankind healthy. Many studies from domestic and foreign countries have focused on acute ischemic brain impairment for many years. But it is insufficiency for research in chronic cerebral hypoperfusion. Recently many trials has indicated that nuclear factor-κB (NF-κB) and cyclooxygenase-2 (COX-2) are two main cytokines which are involved in the ischemic brain injury, but has not yet been recognized the function mechanism of NF-κB , COX-2 on chronic cerebral ischemia.3-n-butylphthalide (NBP) was synthesized and developed as an anti-cerebral ischemia agent, NBP can protect brain tissue from acute cerebral ischemia. In this study using rats, we focus on the mechanism of NF-κB and COX-2 expression in inflammatory reaction following chronic cerebral hypoperfusion. The aim of this study is to explore that mechanism of the protective effect of NBP on inflammatory reaction after chronic cerebra ischemia.Materials and methods100 healthy 12-14 month-old wistar rats whose weight was from 450g to 550g, male or female, were randomly divided into five groups: 20 rats each group. Group A: control group (sham operation); Group B: ischemia group; Group C: ischemia and high dose treatment group; Group D: ischemia and low dose treatment group; Group E: precaution and ischemia. According to Olsson's method, we replicated rats model by blocking bilateral common carotid arteries permanently (2VO) . The rats in group C and group D began to be treated after animal model was constructed for two months. The rats in group A and group B were treated gastricly with the same doses of peanut oil. The rats in group C, group D were given 12mg/100g/d and 6mg/100g/d separately. The rats in group E began to be treated one month before animal model was constructed and they were given 8mg/100g/d. The treatment lasted for one month. We observed hippocampal CA1 square and temporal cortex histomorphology in virtue of optic microscope; NF-κB p65 and COX-2 positive cells were observed through immunohistochemistry technique. The results are expressed as mean±SEM (x±s), The data is analyzed with statistical software of SPSS14.0 using One-way ANOVA and q. The Fishers LSD post hoc test was used to test the differences between two groups. The significant difference was set at P<0.05.Results1. The results of pathological section with HE staining: Only a few degenerated and dead neurons were found, while most neurons were normal in morphology in control group. The number of degenerated and dead neurons significantly increased in ischemia group compared with control group, and normal neurons were less, deformation of neuron bodies and concentration of nucleus and bubble in cytoplasm were more in this group. The number of degenerated and dead neurons was less in post-ischemia treated group than that in only ischemia group.2. The results of immunohistochemistry for NF-κB p65: NF-κB p65 was significantly translocated from cytoplasm into nucleus in ischemia group. However more NF-κB p65 remained in the cytoplasm of control group and NBP groups. NF-κB p65 positive cells in hippocampus CA1 square and temporal cortex in each group: group A: 1.45±0.34, 2.32±0.46; group B:22.72±0.56, 26.18±0.54. The number of NF-κB p65 immunopositive cells in each part were increased markly in group B comparing with group A. The difference between group B and group A was significant (P<0.01). group C: 8.67±0.44, 12.33±0.39; group D: 5.20±0.46, 19.96±0.38; group E: 11.03±0.42,14.04±0.70. The difference of each group was apparent (P<0.01).3. The results of immunohistochemistry for COX-2: COX-2 was significantly increased in ischemia group. After treated of different dosage NBP for one month, COX-2 positive cells decreased in hippocampus CA1 square and temporal cortex in each group, group A: 1.28±0.41, 2.40±0.37; group B: 26.25±0.46,32.00±0.63; group C: 9.00±0.58, 16.41±0.49; group D: 15.05±0.51, 24.36±0.45; group E: 11.24±0.70, 20.23±0.52. The difference of each group was apparent (P<0.01).ConclusionsDropsy and denaturalization of neurons were alleviative in the area of hippocampus CA1 square and temporal cortex by treating of 3-n-butylphthalide; 3-n-butylphthalide decreased the expression of NF-κB p65 and COX-2, 3-n-butylphthalide could suppress inflammation reaction after chronic cerebral ischemia; 3-n-butylphthalide may be protect brain after chronic cerebral ischemic injury; 3-n-butylphthalide may be have a precaution effect after chronic cerebral ischemia.
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