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The Gastrodia Research On Parkinson's Disease Rat Neuron Protection And Mechanisms

Posted on:2008-10-24Degree:MasterType:Thesis
Country:ChinaCandidate:G L XuFull Text:PDF
GTID:2204360212488853Subject:Integrative basis
Abstract/Summary:PDF Full Text Request
Parkinson's disease (PD) is a neurodegenerative disease.It is one of the frequent senile disease in central nervous system.With the increasing ageing of population,PD is one of the main disease to threaten the health of the human being.A major pathological hallmark of Parkinson's disease is a progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and their axons,which project to the striatum.Thus,To lead to PD patient appear the clinical symptom of hypokinesia,rigidity and tremor et al.Up to now,as the disease remains poorly understood,there is still no effective treatment.It is one of the hot subject of studying to use the neuroprotective therapy to prevent and cure PD.The results of the modern pharmacological study showed that gastrodia rhizome or its products have the well efficacy as immunological regulation and anti-apoptosis,which can protect neurons.To elucidate the effect of gastrodin in the behavior,morphology,neurotransmitter , we use the technique of high pressure liquid chromatography(HPLC) and immunohistochemistry,which to help us to reveal the etiopathogenesis of PD and the mechanism of action of the gastrodin in order to prevent and cure PD.Furthermore, to provide theoretical support for clinical medication and have significant theoretical purpose.In experimental research,male SD rats were left-CPU injected with 6-OHDA(20ug)to establish PD model.The experimental animals is divided randomly into six groups:①The normal control group,②The model contral group,③Western medicine contral group,④gastrodin large dose group,⑤gastrodin middle dose group and⑥gastrodin small dose group.The animals were killed on the 14th day after injecting with 6-OHDA.This study is consisted of four parts:①To observe the changes of ethology and pathology in PD rats and the effect of gastrodin.②To study the contents of DA,DOPAC and HVA in striatum in PD rats and the effect of gastrodin by HPLC.③To investigate the expression of TNF-αand GDFN in SNpc and VTA in PD rats and the effect of gastrodin by immunohistochemistry technique.④To observe the expression of Caspase-3 and TH in SNpc and VTA in PD rats and the effect of gastrodin by immunohistochemistry technique.The main results are displayed as follows:1 Gastrodin can improve PD rats'ethologic and morphologic dysfunction. Each group rats that are injected APO after 10 minute appear different d egree motional state,restlessness and foraging,for about 30minuts then come down.The result show that the rotation number in the low dose and madopar group significantly decreased ,comparing with model group, however, large and middle does group no significant difference.Moirris water labyrinth result show that there was significant difference between low goes group and model group(p<0.05).The HE staining result show that the neuronal shape is no change,but the number is slightly decreased and a few neuron are degenerative in rats'SN among each dose gastrodin group。2 Gastrodia can increase the content of DA and its metabolic product in Striatum in PD rats.The content of DA,DOPAC and HVA in model group significantly decreased compared with normal group(p<0.01).The ratio of DA/DOPAC and DA/HVA in model group increased compared with normal group(p<0.05).The content of DA,DOPAC and HVA in low does group significantly increased compared with model group. In treatment groups,the contents of DA,DOPAC and HVA were recovered significantly and the ratio of HVA/DA decreased.3 The expression of TNF-αis decreased and the GDNF is increased in PD rats brain glial cell in each gastrodin-treated group.Image analysis and statistic result display that the expression of TNF-αis significantly increased in the cytoplasm of DA Neurons in VTA and SN in Models group compared with normal group(p<0.01).The low does and madopar group is similar to compared with normal group and declined significantly to compared with model group(p<0.05).Image analysis and statistic result show that the expression of GDNF significantly increased in the cytoplasm of DA Neurons in VTA and SN in middle, small dose group compared with model group(p<0.05).The low does group is significantly increased not only compared with normal group but also madopar group.There was no difference among the other group.4 Gastrodine may protect the loss and apoptosis of TH+ dopaminergic neurons by declining the express of Caspase-3 in SNpc in PD rats.In the experimental studying, immunohistochemistry technique is used.The TH+ dopaminergic neurons were counted in every group.The loss of TH+ neurons are partly inhibited in SNpc of each gastrodin treat group.The number of TH+ neurons in SNpc of small dose group and middle dose group is decreased by 16% and 17%;The number of TH+ neurons in SNpc of madopar group and large dose group is decreased by 22% and 20%.Correspondingly, the number of Caspase-3+ neurons in SNpc in small does and middle does group is obviously decrease d. The trend of decreasing of TH+ neurons is opposite to the change of number of Caspase-3+ neurons.Conclusion:①first,immuni-inflammation and apoptosis may be one of main way in loss of dopaminergic neurons in Parkinson's disease.②Secondly,gastrodin may suppress the lose and apoptosis in SNpc,by adjusting the above factor.The effect of small dose group is best.It is indicated that gastrodin can moderately protect DA neuron and slow down the process of PD.
Keywords/Search Tags:Gastrodin, immuni-inflammation, Apoptosis, Dopaminergic neuron, 6-hydroxydopamine(6-OHDA) rats
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