Ethyl Pyruvate Effects On Ischemia-reperfusion Nrf2-ARE Pathways And Cognitive Function

Objective: To study the effects of Nrf2-ARE pathways in brain isch-emiareperfusion, we observed the effects of ethyl pyruvate on ischemiarep erfusion Nrf2-ARE pathways and mitochondria in neuron, and discussed the effects of ethyl pyruvate protective action on short-term cognitivedysf-unction after cerebral ischemia-reperfusion.Methods: 66 SD rats were randomly grouped into three groups, threegroups are the sham group, the ethyl pyruvate group, and the ischemiareperfusion groups group, each group of 22. The ethyl pyruvate group, and the ischemia-reperfusion groups group were blocked two blood vessels to established the rat model of ischemia-reperfusion brain tissue; the sham group were only separate bilateral common carotid artery, which were not clipped. The ethyl pyruvate group injected immediately ethyl pyruvate in abdomen after restoring blood flow; the others were given the same dose of saline. In each groups, three sets of behavioral tests of cognitive function assessment were tested by morris, the mRNA of Nrf2, HO-1, ?-GCS, NQO1 in hippocampal-neural tissue were detected by PCR, using electronmicroscope to observe the changes of ultrastructure and mitochondrial in the hippocampus nerve cells of three groups.Results: (1) Before modeling, morris test scores of three groups, including escape latency, piercing frequency and the percentage of T-quadrant swimming distance were no statistically significant difference (P>0.05). After building,morris test scores on the 4th and 7th days, escape latency of ethyl pyruvate group and ischemia-reperfusion group significantly prolong than the control group, while piercing frequency and the percentage of T-quadrant swimming distance significantly lower than the control group, differences has statistics meaning (P<0.05), escape latency of ethyl pyruvate group lower than the ischemia reperfusion group, piercing frequency and the percentage of T-quadrant swimming distance of ethyl pyruvate group higher than the ischemia reperfusion group, differences has statistics meaning (P<0.05).(2) The mRNA of Nrf2, HO-1,?-GCS, NQO1 in ethyl pyruvate group and ischemia-reperfusion group content significantly higher than control group, differences has statistics meaning(P<0.05), the mRNA levels of Nrf2, HO-1, ?-GCS, NQO1 in, ethyl pyruvate group higher than the ischemia reperfusion group. (3) In electron microscopic perspective, control group: the morphology of nerve cells more rules, a large number of mitochondria in the cytoplasm, clear and tidy of the crest, distribution withinthe endoplasmic reticulum, ribosome aggregation attach themselves to it,complete nuclear membrane, can clearly see the nucleolus and chromatin,electron microscopy of the electronic display high transparency.Ischemia-reperfusion group: the morphology of nerve cells has changed, Shape is irregular, the mitochondria cristae damage and fracture, a number of modified cavitation, ribosomes have fall off, visible high electron density distribution of particles in the cytoplasm, nuclear membrane rupture, chromatin gathered and uneven. Ethyl pyruvate group: The damage of microstructure in nerve cells lighter than ischemia-reperfusion group, Only a small number of damaged mitochondria, little modified cavitation and little damage forms of endoplasmic reticulum, nucleolus can be seen,a small amount of particles are observed in the cytoplasm,a small number of chromatin concentrate together.Conclusions: (1) Ethyl pyruvate can improve spatial learning and me mory ability after cerebral ischemia reperfusion. (2) Ethyl pyruvate can prot-ect the brain by raising gene expression of the Nrf2-ARE pathways.(3) Ethyl pyruvate can decrease the damage of mitochondria in nerve cells after cerebral ischemia and reperfusion.