Effects Of NAL On The Expressions Of FADD And NF-kB In Rat Model Of Acute ICH

FADD also known as Mortl, is a death domain protein. It was found in the study of signal transduction pathway. It can form a specific binding with the cytoplasm of Fas. So it is called Fas-associated withdeath domain protein. Matsuyama research believes that FADD exposures the FADD N-terminal of the death zone through the interaction of its C-terminal domain of deaths and Fas C-terminal domain of death, and rouses caspase-8, Start the cascade of cell apoptosis, and causes the morphological changes of DNA cells seen under the microscope and the nuclear of apoptosis. Li Yunfeng and other people have researched the expression of FADD in ischemic rat brain cortex cells and believe that the overexpression of FADD has a relationship with the ischemic neuronal cell apoptosis. Xue M and other people used the Rat autologous blood injection method of intracerebral hemorrhage to find that Apoptosis sustain bleeding after four weeks. Zheng fengjin and other people researched and found that there is the expression of FADD in the rat model of cerebral hemorrhage around hematoma, and it could sustain for 72 hours long, and the peak happened 12-24 hours after hemorrhage, and there comes the apoptosis at the same time. The peak happened 1 to 3 days after the bleeding and it descended after 72 hours. The apoptosis of slots also shows a higher degree in the clear expression of FADD. It shows that FADD bleeds after the regulation of cell apoptosis.NF-Kb is a widespread nuclear transcription factor that has diverse functions and participates in a variety of inflammation-related gene expression and regulation. In recent years studies have shown that NF-kB also exist in the brain vascular endothelial cells, neurons and glial cells in the central nervous system. When ischemia happens, it can be activated by specificity, and it is close related with cerebral ischemia-reperfusion injury in inflammatory mechanisms. But scholars at home and abroad on NF-kB did little research on the expression and significance after the intracerebral hemorrhage (ICH). Hickenbottom found that NF-kB increases the expression and has relationship with the cell death after ICH. But they don't know the specific mechanism. Many mechanisms can lead to NF-kB activation and expression after ICH. The research shows that there is ischemic penumbra around organization of the hematoma, and there are cell calcium overload, lipid peroxidation, a large number of ethnic oxygen (ROS), and excitatory amino acid (EAA) in this district. All these factors can effectively stimulate NF - kB activation; coagulation cascade effect can also be generated by PAR-1 thrombin receptor activator of NF-kB; products inside and outside the hematoma interleukin (such as lysosomal enzyme activity and oxygen metabolites, etc.) is also an effective stimulus; inflammatory cytokines (such as TNF-αand IL-1β, etc.) exist around other hematoma can also activate NF-kB. A new study shows that NF-kB increases the expression after ICH, and it can increase various adhesion molecules to participate in secondary brain injury.There was some report about the regulation of FADD on NF-kB signa in the past. In those studies, the temporary increase overexpression of FADD can increase the basic level of activity NF-kB, and it can induce the increase of expression both of the NF-kB dependent gene product of monocyte chemoattractant protein-1 and IL-8. The current research upon FADD evaluates the regulation upon the NF-kB activation. In some studies of the FADD-induced NF-kB activation, FADD did promote the activation of NF-kB. According to the researchers, in the Jurkat cell lines that FADD defect, TNF-α, TRAIL and Fas ligand-induced NF-kB activation was significantly reduced or even disappear, which suggests FADD promote NF-kB activation.Although FADD has been described as the classic precursors of apoptosis signaling molecules, but there are also reports that the excessive expression of FADD will block the activation of LPS upon NF-kB, but the lack of FADD will enhance the activation of LPS on NF-kB. In addition, the two dependent gene products, IL-6 and KC, increase the expression in FADD-/-MEFs compared with the wild-type mice fibroblasts (MEFs). This enhanced activity of NF-kB has relationship with the degradation of IkB. FADD-/-MEFs by IL-1β-induced have resistance against activation of NF-kB. FADD-/-MEFs length in the reconstruction of FADD completely reversed either by LPS or by IL-1β-induced NF-kB activation increase. In short, the evidence shows that FADD reverse conditioning LPS and IL-1β-induced NF-kB activation, and this degradation of IkB regulation in the upstream link. NF-kB is a widespread, diverse function of the nuclear transcription factors, such as Hickenbottom after ICH found increased expression of NF-kB and cell death, but the specific mechanism ominous. ICH after many mechanisms can lead to NF-kB activation and expression. A study shows that NF-kB after ICH in the increased expression, and through increased participation in a variety of adhesion molecules and secondary brain injury.There are some reports about the regulation of FADD on NF-kB signaling in the past. In those studies, FADD temporary increase overexpression of NF-kB the basis of the level of activity, but there are also reports of excessive expression will be FADD blocking LPS-induced NF-kB activation, and the lack of FADD will enhance LPS on NF-kB activation. NAL is a synthetic morphine hydroxyl dihydro-N-allyl derivatives that can inhibit endogenous opioid receptor. When the incidence of ischemic strokes, hypothalamic pituitary large factor on the release of endogenous opioid release of substances (such asβ-endorphin, etc.) from vital organs such as heart and brain dysfunction. Some scholars have also found that endogenous morphine to reduce cerebral blood flow and cerebral oxygen consumption, since the early 1980s, such as Baskin reported NAL to restore the role of cerebral ischemia and hypoxia, have been paid much attention. ICH is neurosurgery and multiple common diseases, brain injury pathophysiological mechanism is not very clear, and there is no effective method of treatment, even if the timely removal of hematoma can not achieve a satisfactory effect, mortality and disability rate remains high. ICH after due to various factors can also lead to around hematoma formation similar ischemic stroke pathophysiological changes in the NAL hemorrhagic stroke protective effect of nerve cells, a study found that NAL is through competitive endogenous opioid antagonist Receptor role to play to protect the function of nerve cells. Since the early 1980s, such as Baskin NAL [20] reported a return to the role of cerebral ischemia and hypoxia, have been paid much attention. FADD and NF-kB in the secondary brain injury in the role of being more and more attention, as NAL intervention after ICH FADD and the expression of NF-kB also not affect the current report.This test used the ICH model which is injected autologous blood coagulation in the caudate nucleus, observed the influence upon the ICH hematoma surrounding area FADD and the NF-Kb expression after the NAL intervention, and explored the ICH NAL brain mechanisms of protection, and FADD and NF - kB correlation. It provides the trial basis for the future treatment of ICH.The results suggest that there appears a small number of positive cells of FADD and more NF-kB positive cells after the treatment of animals NAL hematoma surrounding brain tissue, and there appears a fairly large number of positive cells of FADD and fewer positive cells of NF-kB after the treatment of animals without NAL hematoma surrounding brain tissue. The difference between them has statistical significance. The results of this experiment shows that, the rats with acute intracerebral hemorrhage model NAL treatment can improve the protection of endogenous substances such as NF-kB positive cells in the expression of apoptosis and reduced FADD promoting substances, such as the expression of positive cells. This suggested that the NAL has the neuronal protection in hemorrhagic stroke just as the role it plays in the ischemic stroke.