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Brilliant Blue G Inhibits Inflammasome Activation And Reduces The Disruption Of Blood-spinal Cord Barrier Induced By Spinal Cord Injury In Rats

Posted on:2020-01-08Degree:MasterType:Thesis
Country:ChinaCandidate:X ZhouFull Text:PDF
GTID:2404330596995932Subject:Sports Medicine and Joint Surgery
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Background: Spinal cord injury(SCI)is one of the most serious complications of spinal fractures,with damage under the interface of permanent loss of sensory and motor function.With the development of the world's economic level,the incidence of SCI increases year by year,which not only brings serious physical and psychological harm to the patients themselves,but also causes huge economic burden to the whole society.However,the pathophysiological mechanism of SCI injury is very complex,and there is no definite treatment plan at this stage.Brilliant Blue G-250(BBG),as a P2X7 receptor inhibitor,can inhibit inflammatory responses and improve nerve damage,but the specific mechanism needs to be further explored.The purpose of this study was to explore the protective effect of BBG on SCI and its related mechanisms.Methods: In this study,120 SD rats with body weight of 220-240 g were randomly divided into Sham group(n=40),SCI group(n=40)and SCI+BBG group(n=40).The SCI model of rats was established by means of vascular clipping.Bbsoe Beattiee Bresnahan(BBB)scores were used to observe the motor recovery of rats after SCI at different times(1d,3d,7d,14 d,21d,n=5).HE staining was used to detect the protective effect of tissue and nerve cells after SCI.Western Blot was used to detect the expression of P2X7,NLRP1,NLRP3,ASC,caspase-1,caspase-11,XIAP,and the expression of il-1? and il-18 were evaluated by ELISA to the effect of BBG on inflammatory response after SCI.We used EB(Evans Blue)dye extravasation assay to detect the effect of BBG on blood-spinal cord barrier(BSCB)permeability after SCI.Results: BBB scores and HE staining suggested that BBG could improve motor function recovery scores after SCI and alleviate histopathological injury(P < 0.05).Western Blot indicated that the expression of p2x7,NLRP3,ASC,caspase-11,caspase-1 and XIAP increased after SCI except NLRP1(P < 0.05),and the expression of p2x7,NLRP3,ASC,caspase-11,caspase-1 and XIAP decreased after BBG treatment(P < 0.05).ELISA indicated significantly increased expression of il-1? and il-18 after SCI(P < 0.05),and il-18 and il-1 ? expression decreased after BBG administration(P < 0.05).The permeability of BSCB increased significantly after SCI(P < 0.05),and EB exosmosis experiment showed that BBG intervention could reduce the damage of BSCB(P < 0.05).Conclusion: BBG inhibits the activation of NLRP1 and NLRP3 inflammasomes,inhibits inflammatory reaction,alleviates histopathological injury,improves motor function after SCI,and alleviates the destruction of blood-spinal cord barrier after SCI.
Keywords/Search Tags:spinal cord injury, inflammasome, P2X7, blood-spinal cord barrier
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