| Objective:Glutamate is the main excitatory neurotransmitter in central nerves system for maintaining the normal brain function. But, overdose glutamate was neurotoxic. It was rarely reported that expression of EAAT, mGluR, Akt and PDGF in injured brain tissues of human or animals with Diabetes Mellitus, and some results was contrary. So in this study, after establishing animal model of rats with DM, it was determined that expression of EAAT, mGluR, Akt and PDGF in injured brain tissues of rats with Diabetes Mellitus, and it was also used for explaining the pathogenesis of brain injury.Methods:animal model of DM was established with feeding with high glucose and fat feeds and injection of STZ. After injection, fasting blood glucose was test, it was diagnosed DM when blood glucose was more than 7mmol/L. total RNA was collected after animal was killed, and it was detected that expression of EAAT-1, EAAT-2, EAAT-3, mGlu-4, mGlu-6, Akt/ PKB and PDGF mRNA by RT-PCR methods.Results:RT-PCR results showed that expression of EAAT3 in rats with DM was significantly higher than that in control rats (P<0.05), EAAT-1, EAAT-2 mRNA slightly increased, mGlu-4, mGlu-6, PDGF and Akt/ PKB mRNA was constant. Discussion:until now, pathogenesis of DM was unclear yet, and it was necessary that research of mechanisms of brain injury formation in patients with DM. glutamate transporter was located in the membrane of neuron and glial cell, it transport glutamate into cell, decreased extracellular glutamate concentration, protect neuron from injury. In pathological condition, transport capability of cell decreased, and resulted in the accumulation of glutamate in synaptic cleft and excitatory toxicity. And this study proved that increased EAAT-3 expression in DM rat could exert its antiport function, and aggravate the accumulation of extracellular glutamate and results in neuron injury. Glutamate increases significantly during brain injury development, bind with mGluR and decreases the release of glutamate, relieves the brain injury. It was seldom reported the relationship between mGluRs and brain injury, and this study found that expression of mGluR4 and mGluR6 mRNA was constant in cortex of DM rats, and this suggested that mGluR4 and mGluR6 did not participated in the regulation of nerve cell injury during decompensation stage of DM. Akt signal pathway was related with brain injury, and this study found that expression of Akt/ PKB did not change in DM rat, this suggested that severity of brain injury of DM rats is not significant. PDGF is very important for the growth and development of neuron and glial cell, and it was reported that glycosylation end-production can induced the release of PDGF from endothelial cell. This result showed that PDGF expression did not change and it may suggest that PDGF did not related with brain cell injury during DM development, or PDGF maybe related with the severity of brain injury. Conclusion:in DM condition, the expression of EAAT3 increases in brain tissues after brain injury formation, and this suggested that EAAT-3 is related with development of brain injury in patients and diseased animal with DM, and it can be confirmed that increased EAAT-3 results in the glutamate release, and exert its excitatory toxicity, aggravate the brain injury. The blockage of EAAT-3 signal pathway maybe a now way to cure DM through palliating the brain injury... |
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