Effect of lipoxin receptor agonist BML-111 on the NLRP3 inflammasome after traumatic brain injury in rats

摘要

Objective:To investigate the effect of lipoxin receptor agonist BML-111 on the NLRP3 inflammasome after traumatic brain injury in rats.Methods:Sixty male Sprague-Dawley rats,weighing 280~340 g,were randomly divided into 4 groups(n=15):the sham operation group(group Sham),the traumatic brain injury group(group TBI),the BML-111 treatment group(group BML-111),and the BOC-2 treatment group(group BOC-2).The TBI model was prepared by craniocerebral collision,while the rats in group Sham underwent only craniotomy without collision.Acute traumatic brain injury model was prepared in group TBI,BML-111 and BOC-2.The rats in group BOC-2 were intraperitoneally injected with 50μg/kg of BOC-230 min prior to trauma.Then the rats in group BOC-2 and BML-111 were injected intraperitoneally with 1 mg/kg of BML-111 immediately and 24 hours after trauma.The neurological severity scores(NSS)were evaluated at 3 and 7 days after brain trauma.The protein expression levels of NLRP3,Caspase-1-p20 and active Caspase-3 were determined by Western blot.The content of IL-1βand IL-18 was detected by ELISA assays.The apoptotic cells were analyzed by the TUNEL method.Results:Compared with group Sham,the brain water content and NSS scores in group TBI were increased,and the protein levels of NLRP3,Caspase-1-p20,activated Caspase-3,IL-1βand IL-18 as well as TUNEL-positive cells in the cortex were elevated significantly(P<0.05);compared with group TBI,the brain water content and NSS scores in group BML-111 were reduced,and the protein levels of NLRP3,Caspase-1-p20,activated Caspase-3,IL-1βand IL-18 as well as TUNEL-positive cells in the cortex were decreased(P<0.05);Compared with group BML-111,the brain water content and NSS scores in group BOC-2 were increased,and the protein levels of NLRP3,Caspase-1-p20,activated Caspase-3,IL-1βand IL-18 as well as TUNEL-positive cells in the cortex were up-regulated(P<0.05).Conclusions:The lipoxin receptor agonist BML-111 might attenuate traumatic brain injury in rats by inhibiting NLRP3 inflammasome activation.