Discussion The Protective Effect And Mechanisms Of Resveratrol In The Brain In A Pentylenetetrazole-induced Mice Epileptic Model

Objective: Discussion the protective effect and mechanisms of resveratrol in the brain in a pentylenetetrazole-induced mice epileptic model In-depth study the pathological changes and its molecular mechanism of seizure, and explore new and effective drugs to prevent seizures and subsequently pathological changes.Methods:1 Healthy adult male clean ICR mice 50, Nrf2 knockout mice. Nrf2- /-, ICR background) 10, weighing between 25-35 g.2 Grouping and intervention as follows: ICR mice were divided into five groups: 1.normal control group. NC) 2.solvent group. SOL) 3.group pentylenetetrazole. PTZ) 4.pentylenetetrazole+resveratrol group. P + R) 5. pentylenetetrazole+sirtinol+resveratrol group. P+R+S) 6.Nrf-/-pentylenetetra-zole + resveratrol group pentylenetetrazole. NRF-/-P+R).3 Take the chronic epilepsy model induced by pentylenetetrazol as research subjects. Use Resveratrol, sirtinol as intervention agent,Recording pentylenetetrazole-induced mice seizures Ratings, Morris water maze test mice cognitive and memory abilities, Western Blot detection SIRT1,Nrf2, HO-1 protein expression of hippocampus of mice, utilize spectrophotometry test the level of MDA, GSH in Hippocampus tissue, Transmission Electron Microscope(TEM)observe ultrastructure changes of nerve cells in epileptic mouse hippocampal CA1.Results:1 Behavioral observations: 1) NC group, SOL Group: mouse seizure-free. 2) PTZ group, P+ R group, P+R+S group, Nrf-/-P+R Group: Four groups mice are different degrees of epilepsic seizure during administration, with an overall upward trend of average rating. 3) compared to PTZ group, P +R group was significantly lower level of seizures. 4) Compared with the P + R group,the P+R+S group, the Nrf-/-P+R group, seizures was significantly higher than the former.2 Morris water maze test results2.1 Directional navigation test: 1) During the experiment, the mice showed a shorter average escape latency trends,The NC and SOL group shortened was most obvious. 2) Compared with NC group, SOL group, The escape latency of PTZ group were short lesser. 3) compared to PTZ group, P+R group was more obvious escape latency short. 4) compared with the P+R group, P+R+S and Nrf-/-P+R group escape latency was significantly extended.2.2 The results of space exploration: 1) among the groups, The mice of NC group and SOL group get the most number of acrossing platform aera. 2) Compared with NC group,The SOL group and PTZ group were significantly reduced. 3) compared to PTZ group, P + R group mice were significantly increased number of crossing platform aera. 4) Compared with the P + R group, the mice of P + R + S and Nrf- /- P + R group were significantly lesser number of crossing platform aera, part of the mice with zero.3 The changes of oxidative stress parameters in mice hippocampus tissue3.1 GSH content. 1) among the groups,the average of GSH content in NC group and SOL group were the highest value. 2) compared with the NC group, GSH value in PTZ group were significantly reduced. 3) compared with The PTZ group, The GSH content in P+R group was significantly increased. 4) compared with the P + R group, The P + R + S group and Nrf- /- P + R group GSH value was significantly reduced.3.2 MDA content. 1) Among the groups,The MDA content in hippocampus of in mice of NC and SOL group were the lowest value. 2) Compared with NC group and SOL group, The MDA value in PTZ group were significantly increased. 3) compared to PTZ group, The MDA content in P+R group was decreased significantly. 4) compared with the P+R group, The MDA content in the P+R+S group and Nrf-/-P+R were significantly increased.4 Detect SIRT1, Nrf2, HO-1 expression in hippocampal tissue use Western Blot. 1)In this experiment, The change trends of the expression of The three kinds index is broadly similar. 2) compared with NC group,The protein expression in PTZ group was higher significantly. 3) compared with PTZ group, P+R group was higher significantly. 4) compared with the P+R group, The protein expression in P+R+S group was significantly decreased.5 TEM ultrastructural changes in hippocampal CA1 region: 1)The morphology of neurons, nuclei, chromatin, organelles in NC group and SOL group have no abnormal changes. 2) the abnormal changes accur in all of PTZ group, P+R group, P+R+S group, Nrf-/-P+R group. 3)among them,The P+R group was damaged lightest, The condition in The PTZ and P+R+S group were similar,and more seriously.4)The cell ultrastructure in Nrf-/-P+R group was damaged most seriously.Conclusions:1 Seizures can induce oxidative stress in brain, And then damage nerve cells, cellular structure was destroyed,even death.2 SIRT1 can activate Nrf2-Are signaling pathways, SIRT1-Nrf2-Are signaling pathway has an important role in protecting cells from injury caused by harmful stimuli and consequently oxidative stress.3 The Resveratrol can activate SIRT1-Nrf2-Are signaling pathway,promote expression of antioxidant proteins and then scavenging reactive oxygen species.4 Resveratrol play an important role on antioxidative stress by epilepsic seizures, and than inhibiting the development of cellular pathological changes,reducing seizures level, lower the seizure grade, improve cognition and memory ability and individual prognosis by activating SIRT1-Nrf2-Are signaling pathway.