Xu Hao, Xu Bin, Wang ZhanXiang, Tan GuoWei, Shen ShangHang
Department of Neurosurgery, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei, Anhui, 230001, People's Republic of China,
Childs Nerv Syst. 2015 Feb;31(2):227-34. doi: 10.1007/s00381-014-2613-2. Epub 2015 Jan 7.
Reactive gliosis has been implicated in the pathogenesis of communicating hydrocephalus. Because the activation of Wnt/β-catenin signaling pathway is considered as a significant factor to contribute to brain development, neurodegenerative process, and reactive gliosis, we target this pathway for intervention by using sFRP-l and investigated the expression of β-catenin, cyclin D-1, and glial fibrillary acidic protein (GFAP) in the brain of experimental hydrocephalic rats in terms of protein and gene expression.
Therefore, 30 adult SD rats were randomly divided into the normal group (n = 5), the sham operation group (n = 5), the hydrocephalus group (n = 10), and the sFRP-l group (n = 10). Hydrocephalic rat models were induced by intraventricular injections of 3% kaolin while sFRP-l group was treated by sFRP-l with kaolin injections. The ventricular dilatation was examinated by MRI at 2-week post-operation. After that, β-catenin, cyclin D-1, and GFAP were qualified by Western blot and immunohistochemistry.
According to the result, the expression of β-catenin and cyclin D-1 increased (P < 0. 05) in the brain tissue of the hydrocephalus group compared with that of the sham group, while GFAP expression in the hydrocephalus group is more obvious (P < 0. 05). In the sFRP-l group, the expression of β-catenin and cyclin D-1 and GFAP expression is lower (P < 0. 05) compared with those of the hydrocephalus group. We demonstrated that the Wnt/β-catenin pathway is activated in the experimental hydrocephalic rat brain. sFRP-l inhibited the expression of β-catenin and cyclin D-1 and alleviated reactive gliosis in the hydrocephalic rat brain tissue, while the development of hydrocephalus was delayed.
These results suggest that regulating Wnt/β-catenin signaling pathway may provide new therapeutic methods for hydrocephalic patients.
反应性胶质增生与交通性脑积水的发病机制有关。由于Wnt/β-连环蛋白信号通路的激活被认为是促进脑发育、神经退行性过程和反应性胶质增生的重要因素，我们使用分泌型卷曲相关蛋白-1（sFRP-1）靶向该通路进行干预，并从蛋白质和基因表达方面研究实验性脑积水大鼠脑中β-连环蛋白、细胞周期蛋白D-1和胶质纤维酸性蛋白（GFAP）的表达。
因此，将30只成年SD大鼠随机分为正常组（n = 5）、假手术组（n = 5）、脑积水组（n = 10）和sFRP-1组（n = 10）。通过脑室内注射3%高岭土诱导脑积水大鼠模型，而sFRP-1组在注射高岭土的同时用sFRP-1进行治疗。术后2周通过磁共振成像（MRI）检查脑室扩张情况。之后，通过蛋白质印迹法和免疫组织化学法检测β-连环蛋白、细胞周期蛋白D-1和GFAP。
结果显示，与假手术组相比，脑积水组脑组织中β-连环蛋白和细胞周期蛋白D-1的表达增加（P < 0.05），而脑积水组中GFAP的表达更明显（P < 0.05）。在sFRP-1组中，与脑积水组相比，β-连环蛋白和细胞周期蛋白D-1的表达以及GFAP的表达较低（P < 0.05）。我们证明Wnt/β-连环蛋白通路在实验性脑积水大鼠脑中被激活。sFRP-1抑制了β-连环蛋白和细胞周期蛋白D-1的表达，并减轻了脑积水大鼠脑组织中的反应性胶质增生，同时脑积水的发展被延迟。
这些结果表明，调节Wnt/β-连环蛋白信号通路可能为脑积水患者提供新的治疗方法。
