摘要
目的:探究柚皮苷对更年期抑郁症模型小鼠海马雌激素受体及神经元细胞凋亡的影响。方法:采用双侧卵巢切除(ovariectomy,OVX)联合慢性不可预知温和性刺激(chronic unpredictable mild stress,CUMS)法复制更年期抑郁症模型;将54只雌性昆明小鼠随机分为空白组、模型组(OVX+CUMS组)、假手术组(SHAM组)、雌二醇组(E2组,20.090 mg·kg^(-1)·d^(-1))、柚皮苷组(100 mg·kg^(-1)·d^(-1))、柚皮苷+ICI182780组(100 mg·kg^(-1)·d^(-1)+0.075 mg·kg^(-1)·d^(-1)),每组9只,连续给药21 d;采用悬尾实验和强迫游泳实验观察各组小鼠行为学变化;HE染色观察各组小鼠海马神经元细胞形态变化;免疫组化方法检测小鼠海马区ERα和ERβ阳性细胞表达;蛋白免疫印迹法检测小鼠海马区ERβ、GluR2、CAMKⅡ、NMDAR1、Bad、Bcl-2及Caspase3蛋白的表达。结果:与空白组相比,OVX+CUMS组小鼠静止时间显著增加(P<0.01),小鼠海马神经元细胞排列稀疏、核固缩,ERβ、GluR2、Bcl-2表达降低(P<0.01,P<0.001),NMDAR1、CAMKⅡ、Bad、Caspase3表达升高(P<0.05,P<0.01);与OVX+CUMS组相比,SHAM组、E2组及柚皮苷组小鼠静止时间显著减少(P<0.01),小鼠海马神经元细胞排列相对完整、紧密,ERβ、GluR2、Bcl-2表达升高(P<0.01,P<0.05),NMDAR1、CAMKⅡ、Bad和Caspase3表达降低(P<0.05,P<0.01);与柚皮苷组相比,柚皮苷+ICI182780组小鼠静止时间明显增多(P<0.05),小鼠海马神经元细胞胞体变小,ERβ、GluR2、Bcl-2表达降低(P<0.01,P>0.05,P<0.05),NMDAR1、CAMKⅡ、Bad、Caspase3表达升高(P<0.01,P<0.05)。结论:柚皮苷可能通过激活更年期抑郁症模型小鼠海马区ERβ受体,减轻谷氨酸受体激活引起的神经元细胞兴奋毒性,减少海马神经元细胞凋亡,改善抑郁样行为。
Objective:To explore the effect of naringin on hippocampus estrogen receptor and neuronal cell apoptosis in a mouse model of menopausal depression.Methods:The menopausal depression model was replicated by bilateral ovariectomy(OVX)combined with chronic unpredictable mild stimulation(CUMS),54 female Kunming mice were randomly divided into Blank group,Model group(OVX+CUMS group),Sham operation group(SHAM group),Estradiol group(E2 group,20.090 mg·Kg^(-1)·d^(-1)),naringin group(100 mg·Kg^(-1)·d^(-1)),naringin+ICI182780 group(100 mg·Kg^(-1)·d^(-1)+0.075 mg·Kg^(-1)·d^(-1)),each group of 9 mice were administered for 21 consecutive days.The behavioral changes of each group of mice were observed by hang-ing tail experiment and forced swimming experiment;The morphological changes of hippocampal neurons were observed by HE staining;Immunohistochemical method was used to detect the expression of ERαand ERβpositive cells in the hippocampus of mice;The expression of ERβ,GluR2,CAMKⅡ,NMDAR1,Bad,Bcl-2 and Caspase3 proteins in the hippocampus of the mice was detected by Western blot.Results:Compared with the Blank group,the immobility time of the mice in the OVX+CUMS group was significantly increased(P<0.01),mice hippocampal neurons with a sparsely organized cell arrangement,nuclear se-questration,the expressions of ERβ,GluR2,and Bcl-2 were decreased(P<0.01,P<0.001),and the expressions of NM-DAR1,CAMKⅡ,Bad,and Caspase3 were increased(P<0.05,P<0.01);Compared with the OVX+CUMS group,the im-mobility time of the mice in the SHAM group,E2 group and naringin group was significantly reduced(P<0.01),mice hippocam-pal neuronal cells are relatively intact and tightly packed,the expressions of ERβ,GluR2 and Bcl-2 were increased(P<0.01,P<0.05),and the expressions of NMDAR1,CAMKⅡ,Bad and Caspase3 were decreased(P<0.05,P<0.01);Compared with the naringin group,the quiescent time of the mice in the naringin+ICI182780 group was increased(P<0.05),the smaller cell body of mouse hippocampal neurons,the expressions of ERβ,GluR2,and Bcl-2 were decreased(P<0.01,P>0.05,P<0.05),and the expressions of NMDAR1,CAMKⅡ,Bad,and Caspase3 were increased(P<0.01,P<0.05).Conclusions:Naringin may reduce neuronal cell excitotoxicity caused by glutamate receptor activation,reduce neuronal cell apoptosis and improve depression-like behavior by activating ERβreceptors in the hippocampus in a mouse model of menopause depression.
作者
苏婷
王丽红
于浩
崔悦
张宁
赵德萍
徐红丹
雷霞
SU Ting;WANG Li-hong;YU Hao;CUI Yue;ZHANG Ning;ZHAO De-ping;XU Hong-dan;LEI Xia(School of Pharmacy,Jiamusi University,Jiamusi 154007,China;Traditional Chinese Medicine Hospital of Wuxi,Wuxi 214071,China;Heilongjiang University of Chinese Medicine,Harbin 150040,China;Wuxi Health Higher Vocational and Technical School,Wuxi 214071,China)
出处
《海南医学院学报》
2023年第16期1225-1232,共8页
Journal of Hainan Medical University
基金
无锡市卫生健康委科研项目(M202206)。
关键词
柚皮苷
更年期抑郁症
雌激素受体
细胞凋亡
绝望行为
Naringin
Menopausal Depression
Estrogen Receptor(ER)
Apoptosis
Despair Behavior
