The Expression Of IL-1βand Caspase-3 In Secondary Brain Injury Following STBI In Rats And The Protective Effect Of Glibenclamide

Objective:To construct a model of severe traumatic brain injury(STBI) for rats,then observe the expression of IL-1βand caspase-3 in the injury cortex and to assess it’s water content and actual apotosis cells of injury brain tissues.Most importantly,we want to study if glibenclamide(GBC) could alleviate secondary brain injury after STBI and it’s mechanism.Methods:We adopted a free falling injury method to construct a model of STBI for rats.Seventy-two adult male Sprague-Dawley(SD) rats, weighing 220-270 g, were randomly and evenly divided into four groups,including sham group(n=18),STBI group(n=18),vehicle group(n=18),and GBC group(n=18). Then 18 rat of each group were divided into two parts,10 rat were used for immunohistochemistry,the other 8 for evaluating the brain water content.The GBC group was respectively injected glibenclamide solution intraperitoneally 10 min,6h,12 h,18h;the vehicle group was injected the same volume of vehicle(DMSO) as GBC group at the same time;STBI group only suffered free falling injury to the parietal lobe but drug or DMSO treatment;the sham group didn’t suffer free falling injury but the other procedures was the same as STBI group.We recorded the venous blood glucose 40 min after operation.Each group of rats were raised in the the same methods and environment.All group of rats were killed under deep anesthesia by 10% chloral hydrate 24 h after operation,then used weight-dry method to assess brain water content and immunohistochemistry to detect expressions of IL-1β、Caspase-3 and TUNEL to assess the actual apotosis around the injury brain tissues.All the data obtained were performed statistical analysis with SPSS20.0 software.P<0.05 was considered statistically significant.Results:1. Brain water content:The brain water content in STBI group was significantly higher than sham group at 24 hours after STBI(P<0.01).There is no significant difference between STBI group and vehicle group(P>0.05),but the brain water content was significant lower than vehicle group(P<0.01).2. The expression of IL-1βwas:The expression of IL-1βaround injury brain tissue in STBI group was significantly increased than sham group at 24 hours after STBI(P<0.01).There is no significant difference between STBI group and vehicle group(P>0.05),but the expression of IL-1β was significant lower than vehicle group(P<0.01).3. The expression of caspase-3:The expression of caspase-3 around injury brain tissue in STBI group was significantly increased than sham group at 24 hours after STBI(P<0.01).There is no significant difference between STBI group and vehicle group(P>0.05),but the expression of caspase-3 was significant lower than vehicle group(P<0.01).4. TUNEL:The actually apoptotic cells around injury brain tissue in STBI group was significantly higher than sham group at 24 hours after STBI(P<0.01).There is no significant difference between STBI group and vehicle group(P>0.05),but actually apoptotic cells was significant lower than vehicle group(P<0.01).5. Venous glucose level:For venous glucose level at 40 min after STBI,there is no big difference all groups(P>0.05).Conclusions:1.The brain water content in rats after STBI was significantly increased,but brain swelling was alleviated after treatment with glibenclamide.2.The expression of IL-1βand caspase-3 around injury brain tissue were increased after STBI,but treatment with glibenclamide could decrease there expression.3.The actual apoptotic cells around injury brain tissue were increased,treatment with glibenclamide could alleviate.4.Low dose of glibenclamide have no significant effect on venous glucose level.5.Glibenclamide could alleviate second brain injury though preventing brain swelling and reducing expression of IL-1βand caspase-3 around injury brain tissue,at the same time,it decresed the actual apoptotic cells around injury brain tissue.