静脉输注艾司洛尔对脊髓缺血再灌注损伤大鼠脊髓组织HIF-1α表达的影响

Effects of infusion of esmolol on the expression of hypoxia inducible factor-llz in ischemia-reperfusion injury to spinal cord in rats

目的评价静脉输注艾司洛尔对脊髓缺血再灌注损伤大鼠脊髓组织低氧诱导因子-1α表达（HIF—1α）的影响。方法健康雄性Wistar大鼠36只，体重300～350g，采用随机数字表法，将其随机分为3组（n=12）：假手术组（S组）、脊髓缺血再灌注组（IR组）和艾司洛尔组（E组）。采用夹闭。肾下腹主动脉20min再开放的方法制备脊髓缺血再灌注损伤模型。E组缺血前30min静脉输注艾司洛尔200g·kg^-1·min^-1，输注时间为1h；IR组静脉输注等容量生理盐水，输注时间为1h；S组不阻断腹主动脉，于分离腹主动脉后输注等容量生理盐水，输注时间为1h。再灌注24和48h时随机抽取大鼠6只，采用Tarlov评分法评价后肢运动功能，然后处死大鼠，取L4-5脊髓组织，光镜下观察病理学结果，采用免疫组化法测定HIF-1α表达水平。结果与S组比较，IR组各时点HIF-1α表达上调，Tarlov评分降低（P〈0．05），E组HIF—1α表达上调（P〈0．05），Tarlov评分差异无统计学意义（P〉0．05）；与IR组比较，E组各时点HIF-1α表达上调，Tarlov评分升高（P〈O．05），脊髓病理学损伤减轻。结论静脉输注艾司洛尔可减轻大鼠脊髓缺血再灌注损伤，其机制与其上调脊髓组织HIF-1α的表达有关。

Objective To investigate the effect of infusion of esmolol on expression of hypoxia inducible factor-1 a following spinal ischemia-reperfusion （I/R） in rats. Methods Thirty-six healthy male Wistar rats weigh- ing 300-350 g were randomly assigned into 3 groups （ n = 12 each） ： group [ sham operation （group S） ; group 11 spinal I/R and group m esmolol pretreatment （group E）. Spinal ischemia was produced by cross-clamping of abdominal aorta distal to renal artery for 20 min in I/R and E groups. Infusion of esmolol 200 g ·kg^-1 ·min^-1 was initated 30 min before spinal ischemia and continued for the subsequent 1 h reperfusion in group Ⅲ （E）. In groups S and I/R the animals received equal volumes of NS instead of lidocaine. Neurological behavior was assessed according to Tarlov scoring system at 24 and 48 h of reperfusion. The lumbar segment （ L4,5 ） spinal cord was resected at 24 and 48 h ofreperfusion for microscopic examination .The expression of HIF-1α in spinal cord was detected by immunohistochemistry analysis. Results Compared with group S, the expression of HIF-1α in spinal cord was down-regulated, and Tarlov score was significantly decreased in groups S and I/R. The spinal cord injury was attenuated in group E compared with group I/R. Conclusion Esmolol infusion can protect the spinal cord against I/R injury, and inhibition of the expression of HIF-1α is involved in the mechanism.