The Functionary Mechanism Of NF-κB And The Protective Effect Of Batroxobin After Experimental Intracerebral Hemorrhage

Objective Lately,evidence for an inflammatory response after intracerebral hemorrhage has been reported both in humans and in experimental models of hemorrhage.Despite substantial evidence for such an inflammatory reaction,there are a limited number of studies devoted to examining the pathological role of inflammatory mediators after experimental ICH.NF-kB is a ubiquitous transcription factor and a member of a family of proteins that are critical regulators of a variety of responses,including inflammation.When activated,NF-kB migrates into the cell nucleus, where it binds to specific NF-kB response elements in the promoters of target genes. This results in the transcriptional induction of genes for many proinflammatory substances, such as cytokines,chemokines, adhesion molecules, and inflammatory enzymes.The present study evaluated the presence and activation of NF-kB in relation to cerebral damage induced by intracerebral hemorrhage. Methods We had injected autologous blood 50μl into the right caudate nucleus in rats to make animal model.The male rats were randomly divided into test group and sham group .The rat in the test group were divided into 7 subgroups at 6h,12h,12h,24h,48h,72h,120h after ICH. BBB permeability was measured by Evans-Blue extravasation.Brain water content was determined by the dry-wet weight method.Some rats were pickedup to do optical microscope and electric microscope investigation on perihematoma tissue.and the expression of IL-1βand MMP-9 protein was measured by immunohistochemical method.NF-κB expression was detected by immunohistochemical method and Western blot analysis. Results 1) HE staining showed that the edema of the brain increased gradually when compared with the sham group after ICH. Water content of the brain in the perihematomal brain regions increased gradually and increased sharply (P<0.01) on the first day after ICH when compared with the sham group,on the third day attained the peak. Brain water content changed in parallel with the changes in BBB permeability. 2) IHC analysis revealed that NF-κB expression increased as early as 3h after ICH and enhanced further reaching maximum induction around the third day following ICH.IL-1βexpression augmented as early as 3h after ICH and enhanced further reaching maximum induction around the the second to the third day following ICH.ICAM-1 expression is similar to that of IL-1β.Plentiful MMP-9 positive cells were found in perihematoamal tissue at 12h,24h,48h and 72h after ICH and the numbers were significantly different from those of the sham group(P<0.01). 3) Western blot analysis of NF-κB was in agreement with the...