论文部分内容阅读
目的：探讨Wnt3a在大鼠蛛网膜下腔出血（SAH）后早期脑损伤中对神经发生的作用及其机制。方法将健康雄性SD大鼠70只按随机数字表法分为假手术组、SAH组、Wnt3aⅠ组、Wnt3aⅡ组、Wnt3aⅢ组、Wnt3aⅣ组和DKK-1组。蛛网膜下腔出血的模型通过枕大池自体血注入法建立。应用免疫荧光技术观察各组大鼠海马的神经发生情况，应用蛋白印迹法检测各组大鼠海马中Wnt通路信号分子散乱蛋白-1（Dvl-1）和β-连环蛋白（β-catenin）的表达情况。结果随着Wnt3a剂量升高，各组中BrdU阳性细胞百分率呈上升趋势（P＜0．05），各组中Dvl-1与β-catenin的蛋白表达量也呈逐渐升高趋势（P＜0．05）；给予经典Wnt通路抑制剂DKK-1后，Dvl-1、β-catenin蛋白表达量与阳性细胞百分率均明显下降（P＜0．05）。结论在蛛网膜下腔出血后的早期脑损伤中，Wnt3a可能通过经典Wnt信号通路促进神经发生，对中枢神经系统的修复与保护发挥积极作用。“,”Objective To investigate the effects and possible mechanisms of Wnt3a on the neurogenesis in rats during early brain injury after subarachnoid hemorrhage ( SAH) .Methods A total of 70 adult male SD rats were randomly divided into 7 groups:the sham operation group, SAH group, Wnt3a Ⅰ group, Wnt3a Ⅱ group, Wnt3a Ⅲ group, Wnt3aⅣgroup and DKK-1 group.The SAH model was established by injecting autologous blood into cisterna magna. An immunofluorescence technique was used to detect neurogenesis by investigating the BrdU-positive cells located in the dentate gyrus of the hippocampus of rats.Dishevelled-1( Dvl-1) andβ-catenin expressions were detected with Western blotting.Results After injection of 5, 10, 20 and 40μg/mL Wnt3a into the cisterna magna, the percentages of BrdU-positive cells gradually increased (P<0.05).The expressions of Dvl-1 andβ-catenin protein were also upregulated in a dose-dependant manner (P<0.05).After injection of DKK-1 as an inhibitor of classical Wnt signaling pathway, the percentage of BrdU-positive cells markedly decreased (P<0.05), and the activities of Dvl-1 andβ-catenin were inhibi-ted (P<0.05).Conclusion Wnt3a may have the potential to promote neurogenesis by activating canonical Wnt-sig-naling pathway during early brain injury after SAH, which can contribute to the protection and reparation of the central nervous system.