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Effect of Deoxypodophyllotoxin, An Agent of Plant Origin, on Nervous System

Author: XuPeng
Tutor: GaoRong;XiaoHang
School: Nanjing Medical University
Course: Health Toxicology
Keywords: Deoxypodophyllotoxin DRG neurons DUM neurons Sodium current Patch clamp
CLC: R285.5
Type: Master's thesis
Year: 2009
Downloads: 40
Quote: 0
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Abstract


First part: deoxypodophyllotoxin the rat DRG neurons deoxypodophyllotoxin the toxin (deoxypodophyllotoxin, DOP) is a plant-derived compounds. Anti-tumor, anti-viral, anti-inflammatory, analgesic and insecticidal variety of effects, but its mechanism of drug action is still not deep enough. The anti-inflammatory analgesic and insecticidal role of research suggests that the mechanism of the DOP and nervous system effects, therefore, the study of the pharmacological effects of the drug nerve could help to define the characteristics of its role and to further clarify its pharmacological mechanism. In this study, rat dorsal root neurons (dorsal root ganglion neuron, DRG) model, using whole-cell patch-clamp technique and laser confocal observed DOP electrophysiological properties and regulatory role of calcium ions. The results show that: the DOP reduce the number of action potentials, reduces the excitability of neurons, likely to participate in the action potential formation and dissemination of the basic Na and the of Ca 2 had an impact; voltage clamp experiments showed that the DOP were concentration-dependent inhibition of TTX-S and TTX-R sodium channel, and makes two sodium channel activation curve in the depolarizing direction, while making two sodium channel The steady-state inactivation curve the hyperpolarization direction of mobile, this role play with DOP pharmacological effects of anti-inflammatory analgesic and anti-cancer efficacy play the role of one of the mechanisms; confocal laser experiments show , DOP through the release of intracellular calcium stores Ca 2 and extracellular Ca 2 transmembrane flow two ways, so that the increase in intracellular calcium concentration of DRG neurons described DOP interfering effect on the physiological state of the neuron, and may be interested in the neurons to produce cytotoxic combination DOP infer DOP produced cytotoxicity may have a common mechanism of action studies on other cells produce cytotoxic and mechanisms, This mechanism may be associated with the role of DOP against a variety of tumor cells, is to play one of the mechanisms of the anticancer effects;, DOP role of neurons may cause neurotoxicity, especially DOP is a fat-soluble organic compounds, can be relatively easily through the blood-brain barrier of a mammal, the nervous system has the potential toxicity. Short, DOP mechanism illustrate the role of the nervous system, the drug has medicinal value, but also produce neurotoxic specific use of interest must be considered. Part II: the insect central DUM neurons separation and voltage door control sodium current records in order to explore the DOP role at the similarities and differences between mammals and insects, the American cockroach dorsal unpaired neurons (of dorsal - unpaired median neurons DUM) As a model and comparative studies of rat DRG neurons. Insect DUM neuron physiology research carried out earlier in a foreign country, but due to technical difficulties in the country but failed to get promotion and application. This research by enzymatic digestion and mechanical separation method preparation DUM neurons of DUM neurons Voltage door control and whole-cell patch-clamp the sodium current record, the of DUM neurons separation method and sodium current record provide support and basis for the field of domestic in-depth study of the insect DUM neurons.

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