橙皮苷对抑郁症大鼠海马神经细胞凋亡、GR及NR2B的影响  

Effects of Hesperidin on Apoptosis of Hippocampal Neurons,GR and NR2B in Depression Rats

作　　者：陈曦[1] 曹慧 胡力 Chen Xi;Cao Hui;Hu Li(Department of Pediatrics,Hunan Brain Hospital,Changsha 410007,China;Department of Psychiatry,Hunan Brain Hospital,Changsha 410007,China;Department of Sleep Disorders and Neurosis,Hunan Brain Hospital,Changsha 410007,China)

机构地区：[1]湖南省脑科医院儿少心理科,长沙410007 [2]湖南省脑科医院精神科,长沙410007 [3]湖南省脑科医院睡眠障碍与神经症科,长沙410007

出　　处：《中国药师》2020年第11期2118-2122,共5页China Pharmacist

基　　金：湖南省自然科学基金项目(编号:2019JJ80026)。

摘　　要：目的:探讨橙皮苷对抑郁症大鼠海马神经细胞凋亡、糖皮质激素受体(GR)及N-甲基-D-天冬氨酸受体2B(NR2B)的影响。方法:将36只SD大鼠随机分为6组:正常对照组、模型组、阳性对照组(氟西汀,10 mg·kg^-1)和橙皮苷低、中、高剂量组(40,80,160 mg·kg^-1),每组6只。除正常对照组外,其余各组构建抑郁症大鼠模型,并灌胃给予相应药物,1次/d,连续28d。采用旷场(open field)实验、糖水偏好实验和强迫游泳实验观察大鼠的行为学变化,ELISA法检测海马组织中GR和NR2B含量,TUNEL法检测海马神经细胞凋亡,Western Blotting法检测海马组织中B淋巴细胞瘤-2基因相关X蛋白质(Bax)和B淋巴细胞瘤-2基因(Bcl-2)蛋白的表达。结果:与正常对照组比较,模型组大鼠自由活动次数明显减少,糖水偏好百分比降低,强迫游泳时间明显延长,海马组织中GR含量和Bcl-2蛋白表达水平明显降低,而NR2B含量和Bax蛋白表达水平明显升高,海马区凋亡阳性细胞数明显增多(P<0.05);与模型组比较,阳性对照组和橙皮苷中、高剂量组大鼠自由活动次数明显增加,强迫游泳时间明显缩短,海马组织中GR含量和Bcl-2蛋白表达水平明显升高,NR2B含量和Bax蛋白表达水平明显降低,海马区凋亡阳性细胞数明显减少(P<0.05),且阳性对照组和低、中、高剂量橙皮苷组大鼠的糖水偏好百分比明显升高(P<0.05)。结论:橙皮苷可通过减少神经细胞凋亡和调控GR、NR2B表达发挥抗抑郁的作用。Objective:To investigate the effect of hesperidin on the apoptosis of hippocampal neurons,glucocorticoid receptor(GR)and N-methyl-D-aspartate receptor 2B(NR2B)in depression rats.Methods:Totally 36 SD rats were randomly divided into 6 groups:normal control group,model group,positive control group(fluoxetine,10 mg·kg^-1),hesperidin low,medium and high dose groups(40,80 and 160 mg·kg^-1)with 6 ones per group.Except the normal control group,the other groups constructed depression rats model.Each group was given corresponding drug by gavage once a day for 28 consecutive days.The behavioral changes of rats were observed by open field experiment,sugar water preference experiment and forced swimming experiment;GR and NR2B contents in hippocampus were detected by ELISA method;hippocampal nerve cell apoptosis was detected by TUNEL method;Bax and Bcl-2 protein expressions in hippocampus were detected by Western blot.Results:Compared with those in the normal control group,the number of free activities in the depression model group decreased significantly,the percentage of syrup preference decreased,the forced swimming time was significantly prolonged,the GR content and Bcl-2 protein expression level in hippocampus decreased significantly,while the NR2B content and Bax protein expression level increased significantly,the number of apoptosis positive cells in hippocampus increased significantly(P<0.05);compared with those in the model group,the number of free activities increased significantly in the positive control group and hesperidin middle and high dose groups,the forced swimming time was significantly shortened,the GR content and Bcl-2 protein expression level in hippocampus increased significantly,while the NR2B content and Bax protein expression level decreased significantly,the number of apoptosis positive cells in hippocampus decreased significantly(P<0.05),and the percentage of syrup preference in the positive control group,hesperidin low,medium and high dose groups was significantly increased(P<0.05).Conclusion:H

关 键 词：抑郁症 橙皮苷 海马 细胞凋亡 糖皮质激素受体 N-甲基-D-天冬氨酸受体2B 

分 类 号：R965.1[医药卫生—药理学]