| Objective: Cerebral ischemia, with high mortality and serious disability, is the most common type of cerebral vascular disease. The mechanism of impairment in acute ischemia is so complicated that it is not totally understood. It is the excessive inflammatory reaction residing in necrosis and ischemic region that participates in the complex pathogenesis. Notch is a protein family of conservative transmembrane receptors in a wide distribution. Notch signaling pathway is related with many nervous system diseases by modulating the intercellular reaction. It has been reported that Notch is associated with NF-κB in some way. As a radical factor of inflammation, NF-κB plays an important role in cerebral ischemic pathogenesis. It can be speculated that Notch signaling pathway takes part in the inflammatory reaction that causes the brain damage. Curcumin is extractive confirmed to possess a variety of biological activities including antiinflammatory, antioxidant and anticancer.This study tested the dynamic expression of Notch1 and the relationship between the dynamic expression of Notch1 and NF-κB in rat MCAO modelin order to detect the role of Notch1 in cerebral ischema. Also, this study evaluated the influence of curcumin on brain water content, infarction volume and the expresion of Notch1 and NF-κB to testify the neuroprotective effect of curcumin on cerebral ischemia and the underlying mechanism.Methods: This study included two parts: Part one evaluated the dynamic expression of Notch1 and NF-κB in rat MCAO model. Part two detected the influence of curcumin on brain water content, infarction volume and the expresion of Notch1 and NF-κB.Part one: Male Sprague-Dawley rats were randomly divided into normal control group, sham1 group and MCAO group. Each group was assigned to 5 subgroups randomly: 6 h, 12 h, 24 h, 48 h and 72 h after operation. MCAO animal model was established by modified Longa method. neurological deficit was evaluated at each time point before the rats was sacrificed, 2 or 3 scores were brought into this study. Immunohistochemistry and Westen blot were used to analyse the expression of Notch1 and NF-κB.Part two: Male Sprague-Dawley rats were randomly divided into sham2 group, vehicle control group and curcumin group (80 mg/kg). Curcumin solution was administrated by intraperitoneal injection immediately after MCAO, sham2 group and vehicle control accepted equal volumn 0.01PBS with 0.5M NaOH. The rats, which were evaluated neurological deficit, were sacrificed at 6 h, 12 h, 24 h, 48 h and 72 h after operation. the ischemic brain tissues were used for analyse the expression of Notch1 and NF-κB. At 24 h after operation, brain water content and infarct size was analyzed.Results:1 Notch1 expression in MCAO group is higher than sham group at each time point. The elevation was found at 6 h , peaking at 48 h, and decreased at 72 h, still higher than sham group.2 NF-κB expression in MCAO group is higher than sham group at each time point. the expressive regulation of NF-κB is consistent with the expression of Notch1.3 Brain water content measurement:brain water content in curcumin group was lower than vehicle control group, the difference was statistically significant (P < 0.05) .4 Infarct size analysis:Compared with vehicle control group, curcumin group significantly decreased the infarct size.5 Curcumin's effect on the expression of Notch1 and NF-κB:Curcumin down regulated the expression of Notch1 and NF-κB,the difference was statistically significant(P < 0.05) .Conclusions:Notch1 were induced at the early stage after MCAO, the expressive regulation of Notch1 is consistent with NF-κB. Curcumin protected the brain damage caused by MCAO, decreased the brain water content and infarct size, down regulated the expression of Notch1 and NF-κB. Notch1 could take part in the inflammatory reaction by interacting with NF-κB, curcumin may protect the brain against ischemic injury through down regulating Notch signaling pathway.
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