不同剂量甘露醇对大鼠创伤性脑水肿AQP4表达的影响和意义

Effect and its implication of different doses of mannitol on aquaporin-4 expression after fluid percussion brain injury in rats

目的探讨不同剂量甘露醇对大鼠颅脑液压冲击伤脑水肿AQP4表达的影响和意义。方法成年雄性SD大鼠60只制作颅脑损伤模型,随机分为5组:假手术组(Sham组)、脑损伤组(TBI组)、甘露醇1组(M1组)、甘露醇2组(M2组)、甘露醇3组(M3组)。M1组、M2组、M3组分别于液压冲击后立即按0.5 g·kg^-1、1.0 g·kg^-1、2.0 g·kg^-1于尾静脉注射20%甘露醇,6·h-1。各组动物均于术后24h处死,用干湿重法、免疫织织化学法和Western blot分别测定脑含水量及AQP4表达。结果与Sham组比较,TBI、M1、M2和M3组动物脑含水量和AQP4表达均明显升高(P<0.05);与TBI组比较,M1、M2和M3组脑含水量和AQP4表达明显升高(P<0.05);M1、M2和M3组间脑含水量和AQP4表达比较差异无统计学意义(P>0.05)。结论液压冲击伤性脑水肿AQP4表达呈增高趋势,不同浓度甘露醇均可上调AQP4表达并加重局部脑水肿,呈非剂量依赖性,小剂量甘露醇治疗创伤性脑水肿可能合理。

Objective To investigate the effect of different doses of mannitol on aquaporin-4(AQP4)expression after fluid percussion injury in rats.Methods 60 rats were employed to establish experimental models according to Dixon’s method and randomly divided into five groups:Sham group,Traumatic brain injury group(TBI group),Mannitol 1 group(M1 group),Mannitol 2 group(M2 group)and Mannitol 3 group(M3 group),the later 3 groups of which were administered 20%Mannitol(0.5 g·kg^-1,1.0 g·kg^-1,2.0 g·kg^-1)respectively via tail vein injection.Brain water content and AQP4 expression were observed by dry-wet measure,immunehistochemistry and Western blot at 24h after TBI respectively.Results As compared with sham group,there appeared significant increases in water content and AQP4 protein expression in TBI group,M1 group,M2 group and M3 group.As compared with TBI group,there were significant increases in water content and AQP4 protein expression in M1 group,M2 group and M3 group.However,there was not of significant difference among latter 3 groups.Conclusion AQP4 expression is upregulated following fluid percussion brain injury in rats,and elevated by different doses of mannitol in dose-independent model.Low-dose mannitol may be reasonable for traumatic brain edema.