Abstract:Objective To observe the effect of glibenclamide on brain trauma-induced brain edema in rats with traumatic brain injury and preliminarily explore its related molecular mechanism for the treatment of traumatic brain injury. Methods The traumatic brain injury model was established by Feeney′s free falling impact method.The modeling rats were divided into 3 groups (n=32 each):model group, glibenclamide low dose group (intraperitoneal injection of 5 μg·kg^-1 glibenclamide) and glibenclamide high dose group (intraperitoneal injection of 10 μg·kg^-1 glibenclamide).The other 32 rats were used as sham operation group (open the bone window only without impact processing, and the rest of the operation was the same with modeling group).The rats in model group and sham operation group were administered by intraperitoneal injection of equal amounts of dimethyl sulfoxide (DMSO) for continuous administration of 5 days.The basic situation of rats in each group after operation was observed.Eight rats in each group were executed at 6 h, 1 d, 3 d and 5 d, respectively after operation to determine the water content and content of Evans blue (EB) in brain tissues.Real time fluorescence quantitative polymerase chain reaction (qRT-PCR) method was used to detect the expressions of aquaporin-4 (AQP-4), matrix metalloproteinase 2 (MMP-2) in brain tissues and matrix metalloproteinase 9 (MMP-9) mRNAs.Western blot method was used to detect the expressions of AQP-4, MMP-2 and MMP-9 proteins in brain tissues. Results In model group, the symptoms such as shortness of breath, rapid heart rate and so on appeared, and breathing and heart rate gradually decreased and restored to stable state after treatment of glibenclamide.There was no obvious pathological phenomenon in sham operation group.In model group, water content and EB content in brain tissues was significantly higher than that in sham operation group (P＜0.05), and horizontal activities and vertical activities were significantly lower than those in sham operation group (n＜0.05).Water content and EB content of brain tissues in glibenclamide low dose group and glibenclamide high dose group were significantly lower than that in mode group (n＜0.05), and horizontal activities and vertical activities were significantly higher than those in model group (n＜0.05)with a dose-dependent manner.The expression levels of AQP-4, MMP-2 and MMP-9 mRNAs and proteins in model group were significantly higher than those in sham operation group (n＜0.05), and they in glibenclamide high dose group and glibenclamide low dose group were significantly down-regulated compared with model group (n＜0.05)with a dose-dependent manner. Conclusion Glibenclamide can improve the permeability blood brain barrier, reduce traumatic brain edema, and improve the behavior ability of the rats with brain injury.Its mechanism may be related to the down-regulation of AQP-4, MMP-2 and MMP-9 expressions.