| Objective: Cerebrovascular diseases have the characteristics of high morbility, high rate of mutilation and high mortality; therefore they can do great harm to human health. The patho-physiological mechanisms of cerebrovascular diseases haven't been fully made out till now. Ideal drugs for successful prevention and treatment cerebrovascular diseases still lack according to recent reports. Based on previous study, present study was performed to test the neuroprotective effect of piperphentonamine hydrochloride (PPTA) and investigate the potential underlying mechanisms in focal cerebral ischemia-reperfusion in rats. And this study may have an important implication in piperphentonamine hydrochloride growing to a new creative drug which has independence intellectual property rights for future treatment of patients suffered with cerebrovascular diseases.Methods:There are four parts of the study.1. Sprague-Dawley rats were randomly divided into the sham group, the ischemia-reperfusion group, the PPTA treated group (2.5,5,10 mg·kg-1) and the edaravone treated group (6 mg·kg-1). Rats were subjected to 24h of reperfusion following ischemia for 2h induced by middle cerebral artery occlusion (MCAO). The different doses of PPTA were intravenously administered to rats after 1h of the onset of ischemia. The neurological behavioral test was performed 24h after reperfusion by using the Zea-longa scores. Infarction volumes with TTC-staining and moisture content were calculated. Using global brain ischemia produced by the four vessels occluding method (Pulsinelli,1986), the MORRIS water maze test had been carried out in rats.2. Sprague-Dawley rats were randomly divided into group as some as Part1. Rats were subjected to 24h of reperfusion following ischemia for 2h induced by middle cerebral artery occlusion (MCAO). The different doses of PPTA were intravenously administered to rats after 1h of the onset of ischemia. The changes of water content, the activity of SOD, GSH, NOS and the content of MDA and NO in brain tissue were measured.3.Middle cerebral artery occlusion(MCAO)was employed to establish focal cerebral ischemia-reperfusion model in rats, then IL-1β, TNF-a, Caspase-3 and hsp-70 mRNA expression were measured by Real Time-PCR.Result:1. Focal cerebral ischemia-reperfusion, induced by MCAO, PPTA administration groups(5mg/kg,10 mg/kg) improved neurological deterioration score, compared with model group. PPTA administration indicated by a significant decrease in the infarction volume and brain tissue water content in rats after focal ischemia and reperfusion (P<0.01). PPTA displayed escape latency improvement as indicated by a significant increase in the swimming distance and duration in the target quadrant after global brain ischemia and reperfusion.2. Compared with model group, in addition, less oxidative damage was detected in the PPTA-treated brain of rats, especially with the dose of 10 mg/kg, including the reduction of MDA levels and NOS activity, the increased activity of SOD and GSH which are antioxidant enzymes especially with the dose of 10 mg/kg, including the reduction of MDA levels and NOS activity, the increased activity of SOD and GSH which are antioxidant enzymes.3. Compared with the model group, the expression levels of TNF-a, IL-1β, Caspase-3, HSP70 mRNA in PPTA treated group were distinctively lower. Conclusion:1. Piperphentonamine hydrochloride (PPTA) have the neuroprotective effect2. The neuroprotective effects of PPTA were greatly associated with inhibition of lipid peroxidation reaction and scavenging free radical.3. The neuroprotective effects of PPTA may performan with inhibiting apoptosis and inflammatory reaction.
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