Molemular Mechanism Of The Proply Gallate Reducing Focal Cerebral Ischemia-reperfusion Injury Is Inhibiting The Activity Of NF-κB Via Antioxidation

Ischemic cerebrovascular disease is greatly harm to the society with high incidence, mortality and rate of disability. Ischemia-reperfusion injury is its important mechanism of damage. Oxidant stress is one of the main reason of the jury in ischemia-reperfusion. NF-κB is activised by oxidant stress and initiates a serial genes downstream, among which the focal inflammatory reaction brought by the inflammatory factor do serious harm to brain. Recently, innate immunity, Toll-like receptor, is in focus in the research of ischemic cerebrovascular disease.Therefore, it is important for reducing ischemia-reperfusion jury to suppress oxidant stress and activity of NF-κB, reduce inflammatory reaction. Red peony root 801 is a Chinese formulated product extracted from the red peony root. Its main effect ingredient is propyl gallate which is a kind of antioxidant being approved by FDA USA.The research chooses the middle artery occlusion with filament in rat to model the cerebral ischemia-reperfusion. First, the damage degree of the MCAO model and the protect effect of the propyl gallate are valued by ethology, apoptosis and the level of oxidant stress. Then, the probably protect mechanisms of the propyl gallate are explained using the research result of TLR4-NF-κB and the inflammatory factor downstream on the peri-ischemic region. The finding of the research is just as following:1. The achievement ratio of model is highest, 82.4%, using 0.28mm filament with 0.32～0.34mm tip. The ratio of subarachnoid hemorrhage in model relate with the filament diameter and tip diameter. Being a invasion index for the success of model, the score after reperfusion 24 h has 100% sensitivity and 96.3% specificity.2. the focal ischemia-reperfusion jury is serious, with the MDA level up, the SOD activity down, the positive cell of Tunel increasing after reperfusion 24 h and the positive cell of Nissl staining decreasing after reperfusion 14 d. NSS is rise and the motive function is impairment.3. the propyl gallate is injected after carotid occlusion with 10 mg/kg/d, 20mg/kg/d and 40mg/kg/d respectively. Comparing to the control group, 20mg/kg/d propyl gallate decrease the MDA level, increase the activity of SOD, reduce the positive cell of Tunel, raise the positive cell of Nissl staining. NSS is also down with motive function improved in 20mg/kg/d propyl gallate group.4. the focal cerebral ischemia-reperfusion injury active NF-κB, whose activity reach peak after reperfusion 12 h in peri-ischemic region. The level of COX-2 and TNFαenhance with the former reaching peak after reperfusion 12 h and the latter after reperfusion 24 h. the level of TLR4 and its ligand also enhance, both reach their peak after reperfusion after 24 h.5. being injected after carotid occlusion, propyl gallate suppress the activity of NF-κB, decrease the level of TNF-αand COX-2, reduce the transcription and expression of TLR4 as well as HSP70.The result mentioned above implies: propyl gallate can reduce the oxidant repress injury causing by cerebral ischemia-reperfusion, reduce apoptosis in peri-ischemic region, protect nerval function. It can suppresses the activity of NF-κB, decrease the level of inflammatory factor, decrease the level of HSP70 and TLR4.