Functional Study Of TREK-1Channel In Acute Cerebral Ischemia

Objective:To observe whether TREK-1has protection in the acute cerebral ischemic rat, α-linolenic acid (ALA), the TREK-1channel activator, was injected to the ventricle of the acute cerebral ischemic rat model.Methods: Rat acute cerebral ischemic model was performed by occluded the middle cerebral artery (MCA) using silicon-coated suture, the regional blood flow was checked through Laser Doppler Flowmetry (LDF) and the rats whose regional blood flow decreasing more than30%after occluded was included in the next experiments; the whole experimental animals were separated into five groups and10rats was contained in each group:sham operation group, model group, low dose group (ALA1uM), middle dose group (ALA lOuM), large dose group(ALA100uM); Intervention groups were separately injected ALA luM, ALA10uM and ALA100uM5uL via the rats’ventricle, the sham operation group rats and the model rats were injected the N.S5uL; then the local blood flow was evaluated again after intervention and the neurological function was assesed through Garcia JH scoring method5h after MCA occlusion; decapitated the rat, isolated the basilar artery and the brain, detected TREK-1expression in the cerebral cortex and the basal artery by real-time quantitative PCR and Western Blot,4successive coronal brain slices were obtained from each rat and were stained with red tetrazolium (TTC) to calculate the infarct area.Results:1. The rats’neurological score in model group significantly decrease comparing with sham operation group, the difference is significant (P<0.05); every dose group’s neurological score is increased comparing with model group, there is significant difference in large dose group and medium group(P<0.05). Model group’s local blood flow decreased comparing with sham operation group, there is significant difference(P<0.01); every dose group’s regional blood flow increased comparing with the model group, there were significant difference in the middle and large dose group’s local blood flow increasing(P<0.05). There was no difference comparing model group’s infract volume using TTC with small dose group(P>0.05); there was significant difference between model group and large dose group(P<0.05).2. Real-time PCR results show that the cortex TREK-1gene expression in model group and large dose group increases compared with the sham operation group, there is significant difference(P<0.05); there are no differences in basilar arteries’TREK-1gene expression comparing different dose groups with sham operation group (P>0.05). Western Blot showed that all groups’cerebral cortex TREK-1channel protein express, the expression level in large dose group is the highest and the less are the model group and sham operation group.Conclusions:Performing ALA, the activator of TREK-1, brings benefits to the regional ischemic rats through ventricle injection, including increasing regional blood flow and reducing the infarction volume, which is contribruted to the activation of TREK-1.