NK1受体拮抗剂L-703 606对大鼠创伤性脑损伤保护作用的实验研究

Cerebroprotective effects of NK1 receptor antagonist L-703,606 against traumatic brain injury in rats

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(TBI)的保护作用。方法将63只雄性Wistar大鼠随机分为对照组(7只)、创伤组(TBI组,28只)、L-703,606组(LT组,28只)。TBI,LT组大鼠分别作自由落体创伤模型,应用免疫组织化学和聚合酶链反应(PCR)技术,动态观察经尾静脉给予NK1受体拮抗剂L-703、606(250nmol/kg)0.5,2,6,12,24,48,72h后P物质(SP)的变化规律。结果①免疫组织化学显示:TBI组脑组织SP阳性单位在伤后0.5h开始表达上调,2、6h依次增高,12h达到峰值(P<0.05)后逐渐回落,72h时高于正常水平。与TBI组相比,L-703、606组脑组织SP阳性单位表达在6h即达到高峰,随后持续回落,72h即恢复正常。且在相应的时间点SP阳性单位表达都低于TBI组。②PCR显示:与免疫组织化学结果基本相似,即L-703、606组脑组织SPmRNA表达较TBI组峰值提前,由12h提前至6h,且在相应时间点减少SPmRNA表达。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。

Objective To investigate the cerebroprotective effects of NK1 receptor antagonist L-703 and 606 a gainst traumatic brain injury （TBI） in rats. Methods Sixty-three adult male Wistar rats were randomized into the control group （n=7）, traumatic brain injury group （TBI group, n=28） and the L-703, 606 treated group （LT group, n=28）. For all rats in TBI and LT groups, model of TBI was induced by free falling body. Immunohistochemistry and PCR tech- niques were used to detect the changes of substance P （SP） at specific time spots （0.5,2, 6, 12, 24, 48 and 72h after injury） with or without NK1-receptor antagonist L-703, 606 given via tail vein（250 nmol/kg）. Results ① Immunohistochemistry showed that the positive unit of SP was up-regulated 0.5 h after injury, progressively enhanced from 2 h to 6 h until peaked at 12 h （P〈0.05）; then declined but still remained a higher level at 72 h. In contrast, expression of positive unit of SP in the L-703, 606 group peaked early at 6 h, then persistently declined until resuming normal level at 72 h. At each time spots,LT group showed lower level of SP positive unit as compared with the TBI group. ② Similarly, the outcome of PCR revealed Early peaking of SP mRNA expression （6 h vs 12 h） and lower level of SPmRNA at all time spots in LT group as compared with the TBI group. Conclusion NK1 receptor antagonist L-703,606 may t）e helpful for recovery through reduction of SP expression and brain edema following traumatic brain injury in rats.