Dexras1介导的炎症反应在蛛网膜下腔出血后白质损伤中的作用

Role of Dexras1-mediated inflammatory response in white matter damage after subarachnoid hemorrhage in rats

目的探索Dexras1在蛛网膜下腔出血(subarachnoid hemorrhage,SAH)中促进炎症和参与白质损伤(white matter damage,WMD)的机制。方法将90只成年健康雄性SD大鼠作为研究对象,采用随机抽签的形式将其分为假手术sham组、SAH组、SAH时间点组、SAH+LV-Scramble组、SAH+LV-Dexras1^+组和SAH+LV-Dexras1^-组,每组12只,利用血管内穿刺法构建大鼠在体蛛网膜下腔出血模型,免疫荧光及神经脊髓固蓝染色分别观察各组皮层髓鞘变化,神经行为学评分检测神经功能变化情况;Western blot检测各组Dexras1、TNF-α、IL-1β及MBP的表达。结果与sham组比较,SAH后大鼠脑组织中Dexras1、TNF-α、IL-1β明显升高(P<0.01),MBP明显减少(P<0.01),出现明显的神经功能缺损、脑水肿、髓鞘损伤及炎症细胞浸润;与SAH+LV-Scramble组比较,SAH+LV-Dexras1^+组大鼠脑组织中Dexras1、TNF-α、IL-1β继续升高(P<0.01),MBP进一步降低(P<0.05),神经功能缺损、脑水肿、髓鞘损伤明显加重,炎症细胞浸润也显著增多;而SAH+LV-Dexras1^-组大鼠脑组织中Dexras1、TNF-α、IL-1β明显降低(P<0.01),MBP升高(P<0.05),神经功能缺损、脑水肿、髓鞘损伤明显改善,炎症细胞浸润也显著减少。结论 Dexras1在蛛网膜下腔出血中具有促进炎症反应,从而参与蛛网膜下腔出血后白质损伤的作用。

Objective To explore the mechanisms by which Dexras1 promotes inflammation and participates in white matter damage (WMD) after subarachnoid hemorrhage (SAH). Methods Ninety healthy adult male SD rats were randomly divided into control group (sham group), SAH group, SAH time ponits group, SAH+LV-Scramble group, SAH+LV-Dexras1^+ group, and SAH+LV-Dexras1^- group, with 12 rats in each group. Intravascular puncture was used to establish a rat model of intracranial hemorrhage under subarachnoid. Immunofluorescence assay and Luxol fast blue staining were used to detect myelin changes in each group;Neurobehavioral scores were used to evaluate the changes in neurological function;Western blot analysis was used to detect the expression of Dexras1, TNF-α, IL-1β and myelin basic protein (MBP) in each group. Results Compared with the sham group, Dexras1, TNF-α, and IL-1β were significantly increased in the brain tissue (P < 0.01), MBP was significantly reduced (P < 0.01), and obvious neurological deficits, cerebral edema, myelin sheath injury and inflammatory cell infiltration were observed in the SAH group. Compared with the SAH+LV-Scramble group, Dexras1, TNF-α, and IL-1β in the brain tissue of the SAH+LV-Dexras1^+ group continued to increase (P < 0.01), MBP was further reduced (P < 0.05), and neurological deficits, cerebral edema, and myelin sheath damage were significantly aggravated, and inflammatory cell infiltration was also significantly increased in the group. However, Dexras1, TNF-α, and IL-1β in the brain tissue were significantly reduced (P < 0.01), MBP was increased (P < 0.05), and neurological deficits, cerebral edema and myelin sheath damage were obviously improved, inflammatory cell infiltration was significantly reduced in the SAH+LV-Dexras1^- group. Conclusion Dexras1 can promote the inflammatory response, and thereby participate in white matter damage after SAH.