| Alzheimer disease (Alzheimers diseases AD)is the brain's degenerative disease which occurs in the early period of the old and the elderly age. It is irreversible, progressive, and mainly charactered by the abnormal spirit and behavior.At the late stage, it could endanger the lives of patients. Its rates of incidence and mortality increase year by year. There are several hypotheses on the pathology of this disease. In recent years ,reseachers has found that non-steroidal anti-inflammatory agent has a certain role for the treatment of this disease, thereby the hypothesis called the immune inflammatory disease has come to be the concern of scholars. It belongs to the Dementia in TCM, which thinks that the Ben of this diease is the deficiency of Five Viscera, damp,phlegm and blood stasis as the Biao. Our study put forward to making the herb of dispelling wind and eliminating dampness-Radix angelica tuhuo(Duhuo) as the breakthrough-point, and using non-steroidal anti-inflammatory drugs as the control .Our purpose is to study Radix angelica tuhuo(Duhuo)'s suppression of inflammatory injury of Alzheimer's disease.Objective: Aim to explore Radix angelica tuhuo(Duhuo)'s inhibition of the Aβrat model's inflammatory injury of Alzheimer's disease. By the observation of Radix angelica tuhuo's action on inflammatory cytokines, the pathway of the signal transduction and apoptosis proteins in the model rat's brain,we are to explore the mechanism of action of the herb of expelling wind and eliminating dampness- Radix angelica tuhuo .Methods: Model rates injected with Aβprotein in the hippocampus were separately gavaged with indomethacin, Radix angelica Duhuo, Salvia and saline. After four weeks ,1) By water maze test we observed drugs'action on rats's ability of learning and memory. 2)With light and electron microscopy we observed neurons's changes in model rats'brain.3) Using immunohisto chemical methods measured expression differences of protein- IL-1, IL-6, TNF-a, INOS, NF-κB in rats'brain of different groups. 4)Western-blot tested different imposed factors's impact on apoptotic protein Bcl-2 and Bax in the brains of rats, and through observation of the impact on the p38MAPK signal transduction pathway ,we explored the mechanism of action of Radix angelica tuhuo.Results: After administration, in addition to the model group and sham-operation group, the rates of the other groups were compared with the premedication, which had shown the shortened Escape latency ( P <0.05). It illustrated that the three kinds of drugs can improve the ability of learning and memory of rats suffering from AD. The level of p38 MAPK expression of Duhuo Group and WM Group was lower than of model group ,with significant difference ( P <0.05). The level of p38 MAPK expression of Duhuo group and WM group was lower than of Salvia Group, but the difference was not significant ( P> 0.05). When Salvia group was compared with the model group, the level of the expression of p38 MAPK fell, but the difference is not significant ( p> 0.05). In cytokines, TNF-α, IL-1, INOS and IL-6,NF-κB had a relatively higher level of expression in the model group than of the sham-operation group ,which indicated that Aβprotein injected into the rats'brain significantly increased the secretion of above Cytokines . When the WM group, Duhuo group,and Salvia group were compared with sham-operation group and model group, the difference was significant ( P <0.05), which suggested that the three drugs had significant inhibition of expression of the above indicators in AD rats brain, but the effect was worse than of the sham-operation group (the expression of NF-κin Salvia group is the same as the model group). In comparison among Salvia group, Duhuo group and WM group, the difference had not shown significant meanings (P> 0.05), indicating that the effect of the two drugs in inhibiting the expression of the above indicators were not significantly different ( P> 0.05). In the regulation of apoptosis of proteins in Salvia group, Salvia and Duhuo can increase the level of the expression of bcl-2, inhibit Bax genetic expression and improve the ratio of Bcl-2/Bax; western medicine- indomethacin had a weaker role than the two above drugs,which indicates that indomethacin can inhibit the inflammatory reaction in the brain,but had a weaker role in inhibition of apoptosis than Duhuo and Salvia.Conclusion: 1, Alzheimer disease is based on the deficiency of Five Viscera,and damp and phlegm are Biao of this disease.The herb of Dispelling wind and eliminating damp-Duhuo can act by the intervention of immune injury mechanisms of Alzheimer disease. 2, Duhuo can improve the ability of learning and memory of AD rates ,reduce the inflammatory reaction in the brains of AD rates by inhibiting the expression of cytokines- IL-1, IL-6, TNF-A;It can regulate nuclear transcription factor- NF-Κb and reduce the level of expression of INOS in the brain,thereby it can reduce inflammatory reaction,apoptosis, oxidative stress reaction and the injury of neurons in the brain of rates.Reduce immune inflammatory reaction by inhibition of the signal transduction pathway of P38MAPK and regulating the expression of apoptosis protein so as to inhibit cell apoptosis. |
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