| Objective: Intracerebral hemorrhage (ICH) is one of the most devastating forms of stroke. It is a critical management to promote intracerebral hematoma to absorb and to ameliorate the brain injury around the hematoma secondary to ICH up to now. However, there is few method available to treat it. The mechanism of brain injury secondary to ICH is complicated, the endothelin system and NF-κB may play an important role. It is very significant to find a fully method of treatment to ICH. Sodium ferulate (SF) is the sodium salt of ferulic acid which is the main component of ligustrazine and angelica. SF can dialate blood vessels, inhibit the recruitment of platelet and inflammatory reaction, increase the ability of body's antioxidant and clear away oxygen radicals. The purpose of this study was to investigate the protective effect and mechanism of SF, and PD155080, ETA receptor antagonist, on brain injury secondary to ICH induced by collagenase, and to provide more experimental bases for its clinical use in future. Methods: Wistar rats were randomly divided into four groups:the normal group(Nor), the control group(Con), the SF group(SF) and thePD155080 group(PD).We established the experimental ICH model in rats by stereotaxical injecting quantitative collagenase(0.6U collagenaseⅦ) into their left caudate nuclei. Neurological severity scores, brain water content (BWC), and the levels of endothelin-1(ET-1) were measured. The Histopathological changes including light microscope, electronic microscope and angiography were also observed, and immunhistichemical staining were used to examine the expression of NF-κB and IκBα,in situ hybridization were used to examine the expression of ET-1mRNA and IκBαmRNA, RT-PCR were used to examine the gene expression of ET-1 and ETAR.Results: ⑴ Hematoma was seen in rats with ICH, neurological deficits were seen in all rats.. Both SF and PD155080 can reduce the neurological severity scores and improve the recovery of neurological function .⑵ Brain water content (BWC) increased progressively over the first 6 hours, reach to peak in 24 hours. SF and PD155080 can reduce BWC of ICH rats to a certain extent.⑶ The pathology changes is significant in the experimental ICH rats. SF and PD155080 could improve histopathologic changes, including promoting the hyperplasia of glial and endothelial cells, increasing the number of newborn capillaries and ameliorating cell degeneration and necrosis, ⑷ ET-1 content and expression of ET-1mRNA and ETARmRNA in perihematoma tissues (PHT) were significantly increased in ICH rats. SF and PD155080 can reduce ET-1 content ,ET-1mRNA and ETARmRNA expression.⑸ The expression of NF-κB in PHT was significantly increasedwhile IκBα was weak in control group. In SF group and PD155080 group ,expression of IκBα was enhanced while NF-κB was inhibited. Both SF and PD155080 have no effect on IκBαmRNA expression. Conclusion:SF has neuroprotective effect on brain injury secondary to experimental ICH . The protective role of them to ICH may contribute to the reduced ET-1 content, expression of ET-1mRNA , ETARmRNA , NF-κB protein immunoreactivity and increased expression of IκBα. PD155080 also has protective effects on ICH rats. Key words: Intracerebral hemorrhage, Sodium ferulate, ET-1,ETAR,NF-κB...
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