骨碎补总黄酮对氢化可的松模型小鼠脑内海马NMDAR1、GluR2和CAMKⅡ表达的影响  

Effect of Drynaria total flavonoids on the expression of NMDAR1, GluR2 and CaMK Ⅱ in the brain of hydrocortisone model mice

作　　者：王一同 徐艳明[2] 张智博 孙慧峰[1] 张宁[1,2] 杨波[1] WANG Yi-tong;XU Yan-ming;ZHANG Zhi-bo;SUN Hui-feng;ZHANG Ning;YANG Bo(School of Pharmacy,Heilongjiang University of Chinese Medicine,Harbin 150040,China;College of Jiamusi,Heilongjiang University of Traditional Chinese Medicine,J iamusi 154007,China)

机构地区：[1]黑龙江中医药大学药学院,黑龙江哈尔滨150040 [2]黑龙江中医药大学佳木斯学院,黑龙江佳木斯154007

出　　处：《海南医学院学报》2022年第24期1860-1866,共7页Journal of Hainan Medical University

基　　金：国家自然科学基金面上项目(81673581);国家重点研发计划(2017YFC1700701);黑龙江省属高校科技成果研发、培育项目(TSTAU-C2018020);黑龙江省卫生健康委科研课题(2020-303);黑龙江中医药大学科研基金基金(2018jkcy05,2018pt04,2019BJP01)。

摘　　要：目的:研究骨碎补总黄酮对外源性糖皮质激素氢化可的松致肾虚的阿尔兹海默症(AD)模型小鼠NMDAR1、GluR2、CAMKⅡ蛋白表达的影响,并探讨其机制。方法:KM小鼠随机分成空白组、氢化可的松模型组、抗脑衰胶囊对照组、骨碎补总黄酮组、骨碎补总黄酮+雌激素受体(ER)阻断剂组,每组15只。除空白组外各组均肌肉注射氢化可的松(25 mg·kg^(-1)·d^(-1))造模,采用水迷宫实验、新物体识别实验和跳台实验进行行为学考察,HE染色观察小鼠海马的病理变化,Western Blot检测各组小鼠海马内NMDR1、GluR2和CAMKⅡ蛋白的表达。结果:实验结果显示,与模型组比较,骨碎补总黄酮组小鼠学习记忆能力明显提高,差异具有统计学意义(P<0.01);小鼠海马内NMDR1和GluR2蛋白表达明显上升,差异具有统计学意义(P<0.01);同时CAMKⅡ蛋白的水平明显下降,差异具有统计学意义(P<0.01)。结论:骨碎补总黄酮可能通过ER增强对氢化可的松模型小鼠脑内NMDAR1、GluR2蛋白的表达,减少CAMKⅡ蛋白的表达,减轻对模型小鼠脑组织的损伤而起到神经保护作用,从而达到治疗AD的作用。Objective:To study the effect of total flavonoids of Rhizoma Drynariae on the expression of NMDAR1,GluR2and CAMKⅡ protein in model mice of kidney deficiency induced by exogenous glucocorticoid hydrocortisone and its mechanism.Methods:Kunming(KM)mice were randomly divided into the blank group,the hydrocortisone model group,the anti-brain failure capsule group,the Drynaria total flavonoids group,the Drynaria total flavonoids+ER blocker group,with 15 animals in each group. Except for the blank group,all groups were injected intramuscularly with hydrocortisone(25 mg·kg^(-1)·d^(-1))to create models.The water maze experiment,new object recognition experiment and platform jump experiment were used to conduct behavioral investigations. HE staining was used to observe the pathological changes of mouse hippocampus,and Western blotting detected the expressions of NMDR1,GluR2 and CAMKⅡ proteins in the hippocampus of mice in each group. Results:The experimental results showed that compared with the model group,the learning and memory ability of the mice in the Drynaria fortunei total flavonoids group was significantly improved,and the difference was statistically significant(P<0.01),the expression of NMDR1 and GluR2 proteins in the hippocampus of the mice was significantly increased(P<0.01),and the level of CAMKⅡ protein significantly decreased(P<0.01). Conclusion:The total flavonoids of Rhizoma Drynariae may enhance the expression of NMDAR1and GluR2 protein in the brain of hydrocortisone model mice through ER,reduce the expression of CAMKⅡ protein,and alleviate the damage to the brain tissue of the model mice and play a neuroprotective effect.

关 键 词：骨碎补总黄酮 阿尔茨海默症 NMDAR1 GLUR2 CAMKⅡ ER 

分 类 号：R285.5[医药卫生—中药学]