洗心汤对SAD大鼠脑内tau蛋白O-GlcNAc糖基化修饰相关酶的影响

摘要

Objective:To study the effects of Xixin decoction (XXD) on O-GlcNAc transferase (OGT) and O-GlcNAc glycosidase in O-GlcNAc glycosylation of tau proteins in the brain of rats with sporadic Alzheimer's disease (SAD) and explore the possible mechanism. Methods Male SD rats were randomly divided into sham-operated group, model group, donepezil group, and low-, moderate-, and high-dose XXD groups. After treatment and behavioral test, the rats were sacrificed for detecting the expressions of OGT and O-GlcNAc glycosidase in the brain using immunohistochemistry and Western blotting. Results XXD significantly enhanced the expressions of OGT in the hippocampus of SAD rats and lowered the expression of O-GlcNAc glycosidase (P<0.05 or 0.01). OGT and O-GlcNAc glycosidase expressions showed no significant differences between the model group and donepezil group (P>0.05). Conclusion XXD can regulate the expression of OGT and O-GlcNAc glycosidase to enhance O-GlcNAc glycosylation of tau proteins in the hippocampus of SAD rats.%目的建立SAD动物模型，研究名方洗心汤对SAD模型大鼠脑组织tau蛋白O-GlcNAc糖基化修饰中蛋白质O位N-乙酰葡萄糖胺糖基转移酶（OGT）、和糖苷酶（O-GlcNAcase）的影响，探讨名方洗心汤防治SAD的可能作用机制。方法将SPF级健康雄性SD大鼠随机分为假手术组、模型组、多奈哌齐对照组、名方洗心汤小、中、大剂量组。治疗结束及行为学测试之后，以免疫组化及蛋白印迹方法检测大鼠脑组织tau蛋白O-GlcNAc糖基化修饰过程中OGT、O-GlcNAcase酶表达的变化。结果名方洗心汤能显著提高SAD大鼠海马OGT的表达，降低O-GlcNAcase的表达，组间差异有统计学意义（P<0.05，P<0.01）。多奈哌齐对照组与SAD模型组相比无显著性差异（P>0.05）。结论名方洗心汤能够调节O-GlcNAc糖基转移酶和糖苷酶的表达，从而提高SAD大鼠海马组织tau蛋白O-GlcNAc糖基化修饰水平。