Tweak - Fn14 - The Nf-kappa B Pathway In The Pathological Process Of Cerebral Ischemia Change And Only Strengthen The Intervention Mechanism Of The Formulas

With the further understanding of the nature of the disease, there are many fit points between Chinese and Western medicine,for example, collateral disease theory of Chinese medicine has been given to the meaning of modern medicine to become a successful model of integrative medicine. Poison damage to the brain network pathogenesis proposed modern biology-based research provides an effective treatment for many of the central nervous system diseases such as ischemic stroke, Alzheimer’s disease, Parkinson’s disease. A large number of studies have shown that the very close relationship between traditional Chinese medicine collateral disease theory and microcirculation. The neurovascular unit concept offers a modern medical basis for drug brain collateral damage doctrine.Tumor necrosis factor superfamily (TNFSF) constitute19kinds of ligands and28receptors. Mediated by ligand TNFSF receptor activation in a variety of central nervous system (CNS) diseases such as:multiple sclerosis, disease, in the pathogenesis of cerebral ischemia play an important role. Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a number of TNFSF, it can and cell surface receptors, fibroblast growth factor inducible-14(Fn14) combining to play a biological role. A large number of results show that the interaction between TWEAK and Fn14can activate endothelial cells, astrocytes, neurons and microglial cells on the nuclear factor kappa B (NF-kB) pathway and thus increase the expression of related genes regulated by NF-k B in cell death, the neurovascular unit permeability adjustment and central nervous system inflammatory responses play a physiological or pathological role. Therefore, the variation of the study of TWEAK-Fn14-NF-kB pathway in ischemic brain disease and not only further enrich the NVU, and deepen the wealth of scientific connotation of collateral disease theory and the unique clinical value.Objective:Observation of TWEAK-Fn14-NF-kB pathway in cerebral ischemia in the rat MCAO model of brain tissue in the timing of expression of characteristics, to explore its relationship with the pathological process of ischemic brain injury; and using the Tongluo prescription Tongluojiunao(TLJN) brain injection intervention, to explore ways of TLJN anti-ischemic nerve injury, and further study the drug’s anti-nerve injury mechanisms of TWEAK-Fnl4-NF-k B pathway, and thus the loss for TCM toxic encephalopathy doctrine of modern biology basis. Methods:1. the first manufacturing MCAO rats cerebral ischemia model, the neurological score, respectively, using HE staining and TTC method of MCAO rat brain tissue morphology and infarct area analysis to explore TongluoJiu’nao brain injection intervention each time point morphology, infarct size and improvement in neurological function.2. using immunohistochemistry and immunoblotting namely:Western blot was observed in the MCAO rat cerebral ischemia model of brain tissue of TWEAK, Fn14and NF-k B timing variation at different time points, and then explore of TWEAK-Fn14-NF-KBpath in the pathological process of cerebral ischemia occurred The changes Tongluojiunao brain injection through the pathway to play the role of anti-nerve injury.Results:1. MCAO cerebral ischemia model in rats, neurological score, brain morphology and cerebral infarct volume analysis, we found that neurological deficits increase in the pathological process of cerebral ischemia; brain tissue interstitial and cell line-derivededema, osteoporosis, and reduce the number of neurons, nuclear fragmentation dissolved or eosinophilic change, glial cells and endothelial cell edema, inflammatory cell infiltration with secondary brain tissue bleeding. Tongluojiunao brain injection to improve neurological function, reduce the pathological changes in ischemic brain tissue, significantly reduced the infarct size of brain tissue.2. the pathological process of cerebral ischemia, of TWEAK, Fn14, and NF-kB expression in brain tissue showing significant increase of TWEAK-Fn14-NF-kB pathway involved in the pathological process of cerebral ischemia, Tongluo Recipe-through the brain to save the brain The injection may play a neuroprotective effect by inhibition of TWEAK-Fnl4-NF-kB pathway.Conclusion:1. TongluoJiu’nao injection to more significant improvement of neurological deficit, reduce the morphological changes in the pathological process of cerebral ischemia, reduce the infarct volume, indicating TongluoJiu’nao injection has a more significant role of anti-nerve injury.2. in the pathological process of cerebral ischemia, brain tissue of TWEAK, Fn14, and NF-kB showing timing increased and the trend is more consistent description of TWEAK-Fnl4-NF-kB pathways play a key role in the pathogenesis of cerebral ischemia, cerebral injection of anti-cerebral ischemic injury mechanism and Tongluo save and down the pathway of ischemic brain tissue of TWEAK-Fn14-NF-kB closely related.