依达拉奉对创伤性脑损伤大鼠预后的改善作用

Role of edaravone in alleviating prognosis of rats following traumatic brain injury

目的探讨依达拉奉对创伤性脑损伤(TBI)大鼠预后的改善作用。方法150只健康SD雄性大鼠按随机数字表法分为正常对照组(10只)、TBI组(70只)、依达拉奉组(70只)(依达拉奉注射液剂量5.4mg·kg^-1·d^-1,每日1次腹腔注射,连续应用2周)。分别于伤后6,12,24,48,72h.1,2周共7个时相点(每个时相点10只)监测大鼠神经行为学及运动功能评分变化。处死大鼠收集血清、脑脊液标本,采用放射免疫分析法(RIA)测定血清和脑脊液B-内啡肽和促性腺激素释放激素(GnRH)含量。结果伤后6,12,24,48,72h、1,2周,依达拉奉组神经行为学及运动功能评分较TBI组升高。其中伤后48h,TBI组与依达拉奉组神经行为学评分分别为(8.2±0.9)分和(10.3±0.7)分(PvO.05),运动功能评分为(5.9±1.0)分和(6.9±1.2)分(PV0.05)。正常对照组血清和脑脊液P一内啡肽含量分别为(50.2±9.5)pg/ml和(16.2±2.8)pg/ml,GnRH含量分别为(75.2±11.2)pg/ml和(36.2±10.8)pg/ml。TBI组伤后6,12,24,48,72h、1,2周血清及脑脊液B-内啡肽和GnRH含量均明显升高;依达拉奉组血清及脑脊液P-内啡肽和GnRH含量较TBI组降低。其中伤后72h,TBI组与依达拉奉组血清P-内啡肽含量为(165.2±8.5)pg/ml和(109.5±6.3)pg/ml(P<0.05),脑脊液0-内啡肽含量为(63.3±3.1)pg/ml和(38.2±2.3)pg/ml(P<0.05);血清GnRH含量为(203.7±17.1)pg/ml和(110.4±19.2)pg/ml(P<0.05),脑脊液GnRH含量为(153.0±13.4)pg/ml和(93.2±10.5)pg/ml(P<0.05).结论在TBI急性期及恢复期连续应用依达拉奉可明显降低内啡肽和GnRH水平,有利于减轻大鼠TBI后继发性脑损伤,促进神经和功能恢复,从而改善预后。

Objective To investigate the effects of edaravone on improving the prognosis of TBI rats.Methods A total of 150 SD male rats were divided into normal control group(10 rats),TBI group(70 rats)and edaravone group(70 rats).In the edaravone treatment group,the rats were injected intraperitoneally once a day continously for 2 weeks with the injection dose of 5.4·kg^-1·d^-1.At 6 hours,12 hours,24 hours,48 hours,72 hours,1 week and 2 weeks after injury,the neurobehavioral and motor function scores of rats were monitored respectively,with 10 rats monitored at each time point.Serum and cerebrospinal fluid samples were collected and the levels of p-endorphin and gonadotropin-releasing hormone(GnRH)were determined by radioimmunoassay(RIA).Results In the edaravone group,the neurobehavioral and motor function scores were higher than those of the TBI group at 6 hours,12 hours,24 hours,48 hours,72 hours,1 week and 2 weeks after injury.At 48 hours after injury,the neurobehavioral scores of the TBI group and the edaravone treatment group were(8.2±0.9)points and(10.3±0.7)points,respectively(P<0.05),and the motor function scores were(5.9±1.0)points and(6.9±1.2)points respectively(P<0.05).Meanwhile,the contents of|3-endorphin in blood and cerebrospinal fluid of the normal control group were(50.2±9.5)pg/ml and(16.2±2.8)pg/ml,and the contents of GnRH were(75.2±11.2)pg/ml and(36.2±10.8)pg/ml,respectively.The levels of 0-endorphin and GnRH in serum and cerebrospinal fluid were significantly increased at 6 hours,12 hours,24 hours,48 hours,72 hours,1 week and 2 weeks after injury.The levels of endorphin and GnRH in the edaravone group were lower than those of TBI group.At 72 hour after injury,the levels of 0-endorph in serum in TBI group and edaravone group were(165.2±8.5)pg/ml and(109.5±6.3)pg/ml respectively(P<0.05),and the levels of p-endorph in cerebrospinal fluid were(63.3±3.1)pg/ml and(38.2±2.3)pg/ml respectively(P<0.05).At 72 hour after injury,the levels of GnRH in serum in TBI group and edaravone group were(203.7±17.1)pg/ml and(110.4±19.2)pg/ml respectively(P<0.05),and the levels of GnRH in cerebrospinal fluid is(153.0±13.4)pg/ml and(93.2±10.5)pg/ml respectively(P<0.05).Conclusion During acute and recovery periods after TBI,continuous treatment with edaravone can obviously reduce the levels of p-endorphin and GnRH,which is beneficial to alleviate the secondary brain injury after TBI in rats,promote the recovery of nerve and function,and improve the prognosis.