化瘀通络灸法治疗皮质下血管性痴呆对额叶皮质下白质神经血管单元作用机理研究

There have no effective treatment in Subcortical Vascular Dementia(SVD) now. Demyelination of subcortical white matter is one of the main pathological change. The probable mechanisim is the damage of subcortical neuron-vessel unit. Two vessel-occlusion method is used to build the model of SVD. contrast to donepezil, we observe the effect of with Du meridian points in behavior. We observe morphological difference from frontal lobe and subcortical white matter(corpus callosum and white matter of lateral ventricle) in two treatments. MBP is to checked as special protein of oligodendrocyte with immunohistochemistry and western blot methods to observe the difference in two treatments. GFAP is to checked as special protein of strocyte with immunohistochemistry to observe the difference in two treatments. We are to discuss the effect of Hua Yu Tong Luo moxibustion in the treatment of SVD is that improving the modulatory mechanism of neuron-vessel unit in subcortical white matter which contains blood capillary, glial cell and neuron.

皮质下血管性痴呆（SVD）尚无有效的治疗方法。额叶皮质下白质脱髓鞘是其主要病理改变之一。额叶皮质下神经血管单元受损可能是其主要病理机制。两血管阻断法（2VO）建立SVD大鼠模型，观察督脉经穴为主的化瘀通络灸法治疗该病，与多奈哌齐治疗比较，从行为学角度观察其疗效差异。从额叶皮质、皮质下白质（胼胝体、侧脑室旁白质）病理观察治疗后两者形态学差异。免疫组化、治疗后两者少突胶质细胞特异性蛋白--髓鞘碱性蛋白（MBP）表达差异。免疫组化法观察治疗后两者星形胶质细胞特异性蛋白--胶质纤维酸性蛋白（GFAP）表达差异。从而探讨化瘀通络灸法对SVD额叶皮质下白质毛细血管、神经胶质细胞及神经元共同组成的神经血管单元修复调节机制。

项目组按《资助项目任务书》计划和要求，进一步查新检索了最新相关资料，完善了皮质下血管性痴呆模型的方法以及各项客观评价指标，在开展预实验等相关工作基础之上，分组实验，艾灸处理；完成了SVD模型复制及各项行为学指标检测，完成了艾灸对SVD额叶皮质及其皮质下白质“神经血管单元损害”形态学影响的观察，完成了艾灸对额叶皮质下白质胶质细胞影响的指标测定。结果显示：①术后7 d，改良法组存活率较传统法组高，术后4w、8w，两组的潜伏期均缩短，穿越平台错误次数均增多，但两组间无显著性差异(P＞0.05)，其海马区神经元有相似程度的变性，可见改良法复制血管性痴呆模型优于传统法；②化瘀通络灸法对SVD模型大鼠跳台实验的潜伏期、错误次数及受损的神经元有明显的改善作用；③化瘀通络灸法对SVD模型大鼠额叶皮质神经元及皮质下白质髓鞘超微结构有明显的改善作用；④化瘀通络灸法可上调SVD模型大鼠脑组织皮质及皮质下白质髓鞘碱性蛋白（MBP）、下调其胶质纤维酸性蛋白（GFAP）的表达。初步揭示化瘀通络灸法可能通过改善额叶及其皮质下白质神经血管单元功能，修复髓鞘，从而起到治疗SVD的作用。