罗氟司特对大鼠蛛网膜下腔出血后早期脑损伤及神经炎症反应的影响

Effects of roflumilast on early brain injury and neuroinflammation after subarachnoid hemorrhage in rats

目的探讨罗氟司特对大鼠蛛网膜下腔出血(subarachnoid hemorrhage,SAH)后早期脑损伤(early brain injury,EBI)及神经炎症反应的影响。方法采用枕大池注血法建立SAH大鼠模型。将36只健康清洁级雄性SD大鼠随机分为:假手术组(Sham组,n=12)、模型组(SAH组,n=12)罗氟司特治疗组(n=12)。于SAH后48h、72h,各组大鼠行神经功能评分,激光多普勒检测大鼠局部脑血流量(regional cerebral blood flow,rCBF),ELISA法检测大鼠脑皮层及血液中IL-1β、TNF-α、IL-6的含量。结果 SAH后48h、72h,与SAH模型组相比,罗氟司特治疗组大鼠神经功能评分显著降低,r CBF显著升高,各时间点大脑皮层及外周血液内炎症因子IL-1β、TNF-α、IL-6的含量显著降低,差异均具有统计学意义(均P<0.05)。结论罗氟司特可减轻SAH后EBI,其机制可能是减轻外周及中枢的神经炎性反应,从而改善局部脑血流量。

Objective To investigate the effect of roflumilaston on early brain injury（ EBI） and neuroinflammation after Subarachnoid hemorrhage（ SAH） in rats. Methods Subarachnoid hemorrhage mode was established the by injection with autologous blood into cisterna magna. 36 male SPF SD rats were randomly divided into sham group,SAH group and roflumilast-treatment group. At 48 h and 72 h after SAH,nerve function score and regional cerebral blood flow（rCBF）were detected by laser Doppler,the IL-1β,TNF-α and IL-6 content of peripheral blood were measured by enzyme-linked immunosorbent assay（ ELISA）. Results At 48 h and 72 h after SAH,compared with SAH model group,nerve function score of roflumilast treatment group descended significantly,and r CBF significantly increased. The content of IL-1β,TNF-α and IL-6 in the cerebral cortex and peripheral blood at each time point decreased significantly,and all these differences were statistically significant（ P 0. 05）. Conclusion Roflumilast reduced EBI after SAH,and the mechanism might be through reducing the peripheral blood and central nerve inflammatory reaction,which improved local cerebral blood flow.