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Mechanism Of The Side Yinxingpingchuan Oxygen Stress The Role Of The Pd Mouse Brain

Posted on:2005-12-12Degree:DoctorType:Dissertation
Country:ChinaCandidate:J ZhangFull Text:PDF
GTID:1114360125459456Subject:Integrative basis
Abstract/Summary:PDF Full Text Request
Parkinson's disease(PD) is a chronic neurodegenerative disease of nervoussystem.which is mainly characterized by a progressive degeneration and necrosis ofdopaminergic neurons in substantia nigra(SN), as well as the decrease of dopamine(DA)content in striatum. The theory on the oxidative stress-free radicals play avery important role in the death of dopaminergic neurons in PD, and anti-oxidanttherapyis currently regared as an effective strategy to halt the progression ofPD.Therefore, it is Clinically significant to explore the effective anti-oxidantdrug with mild toxicity.Ginkgo Biloba Pingchan Recipe ( GBPR ) is a complex mixture constituted ofpolypeptides that exhibiting different pharmacological activities. Our previous workfound that Ginkgo Biloba Pingchan Recipe had the effect of clearing out of theoxygen-derived free radicals by in vitro experiments. In addition, Ginkgo BilobaPingchan Recipe resisted to the toxicity of Fe. Whereas, oxidative stress andneurotoxicity of Fe are both involved in the progression of PD. This indicates thatGinkgo Biloba Pingchan Recipe possibly possesses the therapeutic effect on PD. Inthis study, the protective effect of Ginkgo Biloba Pingchan Recipe on dopaminergicneurons in SN and CPu was investigated by the PD model mice treated with l-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP). Meanwhile, the cytomolecular mechanism ofGinkgo Biloba Pingchan Recipe on therapeutic was also studied. In experimental research,male C57BL/6J mice were intraperitoneal injected withMPTP(30mg/kg/day, i.s.c.)for 5days to establish PD model. The modeled mice arecalled Parkinsonian mice.The experimental animals is divided randomly into sixgroups:(1)The normal control group(NC),(2)The model contral group(MC),(3)GinkgoBiloba Pingchan Recipe group(GBPR),(4)Jiedu Recipe group(JDR),(5)Pinggan RecipeGroup(PGR),(6)Huayu Recipe group(HYR).The doses of Ginkgo Biloba Pingchan Recipe andits three similar prescriptions were respectively given for 2 weeks and 4 weeks inthe treatment groups.The animals were killed respectively on the 14th and the 28th dayafter first injecting with MPTP.Animals were examined behaviorally with the poletest consecutively. The brains were then removed immediately and the striatum weredissected out. Contents of Dopamine (DA), dihydroxy-phenyl acetic acid (DOPAC) andhomovanillic acid(HVA)were measured by high performance liquid chromatography withelectrochemical detection (HPLC-EC), MDA, SOD, GSH-Px were measured in forebrainstriatum of model mouse for PD in spectrophotometer. The remained tissue of brainswere fixed with 10% formaldehyde and the coronally 6um-thick sections from英文摘要 5mesencephalon were prepared for immunocytochemistry(ICC).Tyrosine hydroxylase(TH),constitutive nitric oxide synthase (nNOS) , nitrotyrosine (NT)and ferritin(Fn) wereobserved by ICC. The expression of nNOSmRNA were detected by in situ hybridization(ISH). The results are as followings: 1.Ginkgo Biloba Pingchan Recipe(GBPR) and its three similar prescriptionsimproved the dyskinesia of PD miceAll the mice intra peritoneal injected with MPTP showed different disability inpole the test and decrease of spontaneous motor activity, the model group(MPTP+NS ) mice demonstrated dyskinesia, scores obtained from the behavioral test wereincreased significantly compared with Normal control group(NS+Ns), but there wasno different change in Normal contral(NC) group in pole test. While the scores intreatment groups (Ginkgo Biloba Pingchan Recipe(GBPR) and its three similarprescriptions)showed a marked decrease to some degree. Chinese medicine groupsimproved disability in pole test and increased spontaneous motor activity(allP<0.05). But there was no difference among the Chinese medicine groups(P>0.05).2.Ginkgo Biloba Pingchan Recipe(GBPR) and its three similar prescriptionsprotected DAergic neurons in substantia nigra compacta(SNpc)The IC...
Keywords/Search Tags:dopaminergic neurons, free radicals, Ginkgo Biloba Pingchan Recipe, MPTP, NT, Parkinson's disease, oxidative stress
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