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NK-1受体拮抗剂L-703,606在创伤性脑损伤大鼠中的实验研究

The Protection of NK1 Receptor Antagonist L-703,606 Following Traumatic Brain Injury in Rat

【作者】 陈垒

【导师】 刘跃亭;

【作者基本信息】 山西医科大学 , 神经外科学, 2010, 硕士

【摘要】 目的:探讨静脉给予NK1受体拮抗剂L-703,606对大鼠创伤性脑损伤的保护作用。方法:将70只雄性Wistar大鼠随机分为对照组(14只)创伤组(TBI组,28只),L-703,606组(LT组,28只)。TBI,L-703,606组大鼠分别作自由落体创伤模型,L-703,606组大鼠造成右顶叶脑挫裂伤后立即尾静脉给予NKl受体拮抗剂L-703,606(250 nmol/kg Sigma公司),TBI组不予处理,对照组在顶骨相应部位颅骨开窗,暴露硬脑膜,骨蜡封闭骨窗,止血后缝合,不进行撞击,然后都于0.5、2、6、12、24、48、72 h开颅取脑。应用免疫组化技术,动态观察对照组,创伤组,L-703,606组在0.5、2、6、12、24、48、72 h后P物质(SP)表达的变化规律。结果:TBI组大鼠伤后0.5 h脑组织SP阳性单位表达开始上调,2、6 h依次增高,12h达到高峰(P<0.05),以后持续回落,在72h仍保持高位。L-703,606组伤后0.5h SP阳性单位表达也开始上调,随着时间的延长表达持续升高,6h达高峰,然后持续回落,72h基本恢复正常(P<0.05)。L-703,606组在相应时间点SP阳性单位表达明显低于TBI组,差异有统计学意义(P<0.05)。对照,TBI,L-703,606组SP阳性单位表达不同,差异有统计学意义(F=74.181,P<0.01)。对照组伤后0.5、2、6、12、24、48、72 h相互之间SP阳性单位表达无统计学意义(P>0.05)。TBI,L-703,606组伤后0.5、2、6、12、24、48、72 h之间SP阳性单位总体有统计学意义(P<0.01)。TBI组6h和24h、0.5h和48h SP阳性单位表达无统计学意义(P>0.05)。时间和分组之间有交互效应(F=3589.696,P<0.01)。结论:NK1受体拮抗剂L-703,606能减少大鼠创伤性脑损伤后SP的表达,减轻脑水肿,并能促进其恢复。

【Abstract】 Objectives:To investigate the protection of NK1 receptor antagonist L-703,606 after traumatic brain injury in ratMethods:seventy adult male Wistar rats were randomized into control group, traumatic brain ingury group and L-703,606 group.The model of free falling body was proceed in TBI,and L-703,606 groups.The group of L-703,606 was immediately administrated NK1-receptor antagonist L-703,606 by vena caudalis after giving traumatic brain injury in right parietal lobe, TBI group was not treated, control group was Opened the skull translation in the same place and Exposed dura, Bone window was closed by Bone wax. Scalp was sutured After bleeding was stoped, Brain was not impacted. All groups was taken the brain at 0.5、2、6、12、24、48、72 h. Immunohistochemistry method were used to observe and detect the changes of SP on specific time spots 0.5,2,6,12,24,48,72h in control group,TBI,and L-703,606 group.Results:Immunohistochemistry showed that positive unit of SP in TBI group was up-regulated 0.5 hour after injury, progressively enhanced from 2h to 6 h, peaked at 12 h,and descend in the rest time, remained a higher level at 72 h.Unlike the TBI groups,the expression of positive unit of SP in L-703,606 groups was peaked at 6 h, continuing descended in the subquent time,recoveried at 72h(P<0.05)。The positive unit of SP in L-703,606 groups at the same time was less than the TBI groups. They also have significant difference (P<0.05)。hey have different positive unit of SP between control groups, TBI groups and L-703,606 groups. Statistics showed they have significant difference (F=74.181, P<0.01)。The control groups did not have significant difference among 0.5、2、6、12、24、48、72 h (P>0.05)。Generally,the expression of positive unit of SP in L-703,606 groups and TBI groups had significant difference at 0.5、2、6、12、24、48、72h(P<0.01)。The positive unit of SP in TBI groups at 6、24、0.5、48 h did not have significant difference(P>0.05)。Time and packet had Interaction effect. (F=3589.696, P<0.01)。Conclusion:NK1 receptor antagonist L-703,606 can reduce the expression of SP following traumatic brain injury in rat,decrease brain edema and hasten recovery.

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