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Effects Of Paeonol On Rat Brain Ischemia-reperfusion Injury And NMDA Receptor

Posted on:2008-05-04Degree:DoctorType:Dissertation
Country:ChinaCandidate:J B WuFull Text:PDF
GTID:1114360242455503Subject:Aquatic products processing and storage
Abstract/Summary:PDF Full Text Request
Ischemic cerebrovascular disease(ICVD)is a common and multiple diseases, which has a serious impact on human health and the lives . It is always the research focus on study the mechanism of cerebrovascular disease and look for the efficacious drugs actively. As we know, today the therapy of thrombolysis and brain protection for ischemic cerebrovascular disease is epidemic trend all the same. Now because of the good curative effect in the treatment of the ischemic cerebrovascular diseases, Chinese traditional medicines have been pay more and more attention to by lots of researchers. Paeonol, a major phenolic component of Moutan Cortex, as Chinese traditional medicine, has been described to possess analgesic, sedative, anti-inflammatory, anti-allergic and antimicrobial properties. In recent years, some studies indicate that paeonol has a protective effect on cerebral ischemia. But no paeonol on rat hippocampal neurons in the oxygen-glucose deprivation and reperfusion injury protection coverage. Our study is to further investigate the protective effects of paeonol on cerebral ischemia-reperfusion injury in rats. and explore the effects of paeonol on NMDA receptors in rat hippocampal neurons. On one level, elucidate the underlying protective effect mechanisms. of propofol on cerebral ischemia in rats.This study is divided into two parts. Ischemia-reperfusion injury in rat brain in vivo and Rat neurons cultured in vitro. The protective effects of Paeonol on focal cerebral ischemia-reperfusion injury in rats are observed in the first part. Rats were randomly divided into 6 groups: Sham-operated group, Model group, Chuanxiong Qin group (100 mg kg-1), Paeonol high. middle.low-dose group (150, 100, 50 mg ? kg-1); The models of focalbrain ischemia-reperfusion injury were established by middle cerebral artery occlusion in rats, ischemia for 2h and reperfusion for 22h. Preventive intraperitoneal injection 3d before modeling, and after modeling 2h and 12h intraperitoneal injection again. 24 hours after ischemia-reperfusion, the rat nerve function scores and the infarct size were measured, brain histopathological changes were observed, superoxide dismutase (SOD). Glutathione peroxidase (GSH - Px), malondialdehyde (MDA) and catalase (CAT) content in ischemic brain tissue homogenate were determined by Spectrophotometric. The results showed that paeonol can reduce the neurologic deficit score in rat MCAO model, and narrow the infarct volume, light cerebral ischemia-reperfusion injury pathological tissue injury, increased SOD, GSH - Px. CAT, reduced MDA in ischemic brain tissue, Compared with the model group with significant differences (P <0.01). Suggested that paeonol has a protective effect on the focal cerebral ischemia-reperfusion injury nerves, reduce oxidative damage may be the mechanism to protect the brain.Whether paeonol has directly protective effects on individual neurons in the brain was observed in the second part through the use of primary rat neurons in vitro culture, ruling out live endocrine, circulation and the impact of a variety of factors, such as body fluids. This study was performed in the rat hippocampus as the object of study, the changes of brain cells with the NMDA receptor subjected to ischemia and hypoxia, the NMDA receptor changes and the impact of paeonol on its own channel was observed. The oxygen-glucose deprivation and reperfusion injury hippocampal neuron survival, NMDA receptor binding, NR1 subunit mRNA expression, cellular excitatory amino acid concentration and intracellular calcium concentration changes in nerve cells, SOD, MDA and NO content and NOS activity were meatured in this paper. The results showed that 1. Paeonol can protect hippocampal neuron from ischemia-reperfusion injury, resulting in alleviating morphological damage and increasing neuron viability. 2. Paeonol blocked NMDA receptor-mediated neurotoxicity pathway by decreasing binding force of NMDA receptors, down-regulating the expression of NR1 submit, decreasing calcium concentration in neuron and reducing content of glutamate, 3. By the treatment of paeonol, the concentration of SOD was increased, then the MDA and NO were decreased respectively; the activity of NOS was also decreased.In short, paeonol play a role in protecting brain as involved in a number of fields. Paeonol as a traditional Chinese medicine with a variety of activities, which gradually attracted the attention of the medical community in recent years, in particular, cardiovascular and cerebrovascular diseases showed good pharmacological activity. We hope this study can provide some help for the clinical application to the research and to the development of new formulations...
Keywords/Search Tags:paeonol, ischemia-reperfusion injury, Hippocampal neurons, NMDA receptor, rats
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