摘要
目的探讨鼠尾草酸对产后抑郁小鼠模型的治疗作用。方法选取雌性C57BL/6小鼠70只行双侧卵巢去势手术,后激素撤退模拟妊娠制备产后抑郁模型。根据糖水偏爱试验筛选50只产后抑郁模型小鼠,随机分为模型对照组,雌激素组(20μg·kg^(-1),sc),鼠尾草酸低、中、高剂量组(25、50、100 mg·kg^(-1),ig)。另取10只雌性C57BL/6小鼠行假手术作为假手术对照组。给药组每日给药1次,连续28 d,给药体积20 mL·kg^(-1)。末次给药后进行糖水偏爱、强迫游泳及自主活动等行为学试验评价抑郁样行为,酶联免疫吸附试验(ELISA)检测血清中成纤维生长因子9(FGF9)、雌二醇(E2)及海马组织中5-羟色胺(5-HT)、脑源性神经营养因子(BDNF)含量。Western blot检测小鼠海马组织中BDNF、FGF9蛋白表达。苏木精-伊红(HE)染色法观察小鼠海马组织CA1区组织病理改变。结果与假手术对照组比较,模型对照组小鼠行为学检测中糖水偏爱指数显著下降(P<0.01),强迫游泳不动时间显著增加(P<0.01),小鼠运动总路程和平均速度显著减少(P<0.01)。海马组织CA1区神经元细胞散乱分布,细胞形态异常,神经元碎片化。ELISA法检测发现血清E2及海马组织中5-HT、BDNF含量显著下降,FGF9含量显著上升(P<0.05或P<0.01)。Western blot法检测发现BDNF蛋白表达下降,FGF9表达升高(P<0.05或P<0.01)。与模型对照组比较,在给予鼠尾草酸治疗后,各组小鼠糖水偏爱指数增加(P<0.01)。雌激素组及鼠尾草酸中、高剂量组小鼠游泳不动时间减少,自主活动的运动总路程和平均速度增加(P<0.05或P<0.01);海马组织神经元损伤程度减轻,细胞排列紧密,形态正常化。雌激素组血清E2水平显著升高(P<0.05),雌激素组及鼠尾草酸各剂量组海马5-HT含量均有不同程度的增加(P<0.01)。雌激素组及鼠尾草酸中、高剂量组能显著降低FGF9含量(P<0.05)。雌激素组和鼠尾草酸高剂量能显著增加BDNF含量,上�
Objective To determine the therapeutic effect of carnosic acid on postpartum depression mouse model.Methods Totally 70 female C57BL/6 mice were selected to undergo bilateral ovarian castration surgery,before hormone withdrawal to simulate pregnancy to create a postpartum depression model.Fifty postpartum depression model mice were screened based on the surgar preference test and randomly divided into a model control group,an estrogen group(20μg·kg^(-1),sc),and low,medium,and high dose carnosic acid groups(25,50,and 100 mg·kg^(-1),ig).Another 10 female C57BL/6 mice that underwent sham surgery served as the sham-operated control group.The administration group was administered once a day for 28 consecutive days,at 20 mL·kg^(-1).After the last dose,behavioral tests such as sugar preference,forced swimming,and open field test were conducted to evaluate depression-like behaviors.Enzyme-linked immunosorbent assay(ELISA)was used to detect the fibroblast growth factor 9(FGF9)and estradiol(E2)in the serum,and 5-hydroxytryptamine(5-HT)and brain-derived neurotrophic factor(BDNF)in the hippocampal tissue.BDNF and FGF9 expressions in the mice hippocampus tissue of different groups were detected by Western blot.Hematoxylin-eosin(HE)staining was used to observe the pathological changes in the CA1 area of the mouse hippocampal tissue.Results Compared with the shamoperated control group,the surgar preference rate of the model control group was significantly decreased(P<0.01),the immobility time of forced swimming was increased(P<0.01),and the total distance and average speed of the mice were decreased(P<0.01).The neuronal cells in the CA1 region of the hippocampus were scattered,with abnormal morphology and fragmentation.ELISA showed a significant decrease in the serum E2,5-HT and BDNF levels in the hippocampal tissue,and a significant increase in the serum FGF9 levels(P<0.05 or P<0.01).Western blot showed that the expression of BDNF protein decreased and FGF9 increased(P<0.05 or P<0.01).Compared with the model control group,a
作者
兰前清
赵丞
王小青
王宇红
姜德建
LAN Qian-qing;ZHAO Cheng;WANG Xiao-qing;WANG Yu-hong;JIANG De-jian(Science and Technology Innovation Center of Hunan University of Traditional Chinese Medicine&Hunan Key Laboratory of Traditional Chinese Medicine Prevention and Treatment of Depressive Diseases,Changsha 410000;Hunan Key Laboratory of Drug Efficacy and Safety Evaluation&Hunan Drug Safety Evaluation Research Center,Changsha 410331)
出处
《中南药学》
CAS
2024年第3期633-640,共8页
Central South Pharmacy
基金
湖南省企业科技创新创业团队(No.2021)。
关键词
鼠尾草酸
产后抑郁
作用机制
动物模型
carnosic acid
postpartum depression
mechanism of action
animal model
