当归芍药散对STZ诱导的糖尿病雌性小鼠认知障碍和雌激素α受体O-GlcNAc糖基化的影响  

Effects of Danggui Shaoyao San on cognitive dysfunction and the changes of O-GlcNAcylation of estrogen alpha receptor in STZ induced diabetic female mice

作　　者：石晶晶 郝徐艺 胡甜 章时杰 李伟荣[1] 王宏[1] 王奇[1] 陈云波[1] SHI Jing-jing;HAO Xu-yi;HU Tian;ZHANG Shi-jie;LI Wei-rong;WANG Hong;WANG Qi;CHEN Yun-bo(Science and Technology Innovation Center,Guangzhou University of Chinese Medicine,Guangzhou 510405,China;Second Clinical Medical College,Guangzhou University of Chinese Medicine,Guangzhou 510405,China)

机构地区：[1]广州中医药大学科技创新中心,广州510405 [2]广州中医药大学第二临床医学院,广州510405

出　　处：《中华中医药杂志》2021年第9期5199-5205,共7页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金项目(No.81674040,No.81573638,No.81673627);广州市科技局项目(No.201805010005)。

摘　　要：目的:探讨当归芍药散是否通过影响脑内雌激素α受体(ERα)的O-GlcNAc糖基化水平从而改善链脲佐菌素(STZ)诱导的雌性糖尿病小鼠的认知功能障碍。方法:采用STZ诱导制备糖尿病小鼠模型,75只C57/BL6雌性小鼠随机分为对照组,模型组,当归芍药散高、中、低剂量组,每组15只,连续灌胃8周,期间监测饮水量、饮食量和体质量;灌胃结束后进行葡萄糖耐量和胰岛素耐量检测;Morris水迷宫、新物体识别实验检测小鼠空间学习记忆能力;Western blot和免疫荧光测定脑组织中ERα含量的变化;Western blot检测O-Glc NAc糖基化相关指标O-Glc NAc、OGT和OGA含量的变化;β-半乳糖苷酶染色观察大脑衰老神经细胞的结构和数目。结果:与模型组比较,当归芍药散高剂量组饮水量、饮食量减少(P<0.01,P<0.05),OGTT曲线下面积显著降低(P<0.01);当归芍药散中、高剂量组体质量增加(P<0.01),逃避潜伏期缩短(P<0.01),新物体识别指数升高(P<0.01),脑组织中ERα、OGA含量显著升高(P<0.01),O-Glc NAc、OGT含量降低(P<0.01),脑组织中衰老细胞减少。结论:当归芍药散可明显改善糖尿病小鼠糖耐量受损及认知障碍,其机制与增加脑内ERα含量及降低O-Glc NAc水平有关。Objective: To investigate whether Danggui Shaoyao San(DSS) can improve the cognitive dysfunction of female diabetic mice by improving the abnormal of O-GlcNAcylation of estrogen alpha receptor(ERα). Methods: The diabetic model was made by streptozotocin(STZ), 75 C57/BL6 female mice were randomly divided into blank control group, model group,DSP high, medium and low dose groups, 15 mice in each group, which were given gavage continuously for 8 weeks, during which the amount of water, diet, and weight were monitored. After the end of the gavage, the glucose tolerance and insulin tolerance were measured, and the Morris water maze method and new object recognition experiment were used to detect the changes in the spatial learning and memory ability of the mice. The changes of ERα in brain tissue were measured by Western blot and immunofluorescence;and the changes of O-GlcNAc glycosylation index, O-GlcNAc glycosyltransferase(OGT) and O-GlcNAc glycosidase(OGA) were measured by Western blot;β-galactosidase staining of brain tissue sections to observe the structure and number of brain aging neurons. Results: Compared with the model group, in the DSS high dose group, the drinking water,diet volume were decreased(P<0.01, P<0.05), and the area under curve of OGTT was significantly decreased(P<0.01);in the DSS high, medium dose groups, the weight was increased(P<0.01), the escape latency was shortened(P<0.01), the new object recognition index was increased(P<0.01), the contents of ERα and OGA were increased(P<0.01), the contents of O-GlcNAc and OGT in brain tissue were decreased(P<0.01). The senescent cells of brain decreased. Conclusion: DSS can significantly improve impaired glucose tolerance and cognitive impairment in diabetic mice, and its mechanism is related to increasing the content of ERα and reducing the level of O-GlcNAc in the brain.

关 键 词：当归芍药散 糖尿病脑病 认知功能障碍 雌激素Α受体 O-GlcNAc糖基化修饰 

分 类 号：R285.5[医药卫生—中药学]