参归仁合剂对激素停撤产后抑郁模型大鼠海马齿状回神经元形态、数量及凋亡的影响  

Effects of Shenguiren Mixture on the Morphology,Number and Apoptosis of Hippocampus Dentate Gyrus Neurons in Rats Model with Postpartum Depression Induced by Hormone Withdrawal

作　　者：周科宇 宋丹 谢萍[1] Zhou Keyu;Song Dan;Xie Ping(Hospital of Chengdu University of Traditional Chinese Medicine,Chengdu 610072)

机构地区：[1]成都中医药大学附属医院,成都610072

出　　处：《中药药理与临床》2020年第5期143-149,共7页Pharmacology and Clinics of Chinese Materia Medica

基　　金：国家自然基金面上项目(编号:81674017)。

摘　　要：目的:探讨补虚化瘀方药参归仁合剂对激素停撤产后抑郁模型(hormone withdrawal models,HWM)大鼠海马齿状回(dentate gyrus,DG区)神经元形态、数量及凋亡的影响。方法:实验选用101只SPF级SD大鼠,按其体重随机分为空白对照组、假手术对照组及模型对照组,模型对照组大鼠行双侧卵巢去势手术,术后合格模型对照组大鼠行激素停撤制备产后抑郁模型。根据空场实验(open filed test,OFT)得分将模型对照组大鼠随机分为模型对照组、雌二醇10μg/只组、舍曲林4.5 mg/kg组、参归仁3.6 g/kg组及参归仁3.6 g/kg+LY2940021.2 mg/kg组,后分别药物干预14 d。给药结束后取大鼠脑海马组织,采用苏木精-伊红(hematoxylin-eosin,HE)染色法及尼氏染色法评价大鼠海马DG区神经元的形态及数量;蛋白质印迹法(Western Blot,WB)测定大鼠海马组织Bcl-2、Bax、Bcl-2/Bax比值及Cleaved-Caspase3的蛋白表达;原位末端转移酶标记(Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling,TUNEL)法检测海马DG区神经元细胞凋亡情况。结果:与空白对照组相比,模型对照组海马DG区颗粒细胞及尼氏小体数量显著减少(P<0.01)、发生变性或坏死等病理改变,海马组织细胞凋亡百分率显著增高(P<0.01),Bax蛋白表达上调,Bcl-2/Bax比值降低。在给予参归仁合剂3.6 g/kg治疗后,大鼠海马DG区未见明显病理改变(P<0.01),海马组织内凋亡百分比显著降低(P<0.01),Bax、Bcl-2、Cleaved-caspase3蛋白表达下调(P<0.05)。与参归仁3.6 g/kg组相比,参归仁3.6 g/kg+LY2940021.2 mg/kg组大鼠海马DG区颗粒细胞及尼氏小体数量显著减少(P<0.01),凋亡情况未见明显差异。结论:补虚化瘀方药参归仁合剂可改善大鼠海马DG区神经元数量、形态及凋亡情况,其作用机制可能通过PI3K信号通路实现。Objective:To investigate the effects of Shenguren mixture(a Buxuhuayu prescription)on the morphology,number and apoptosis of hippocampus dentate gyrus(DG)neurons in hormone withdrawal rat model(HWM).Methods:101 SPF-grade SD rats were randomly divided into the control group,the sham operation group and the model group according to their body weight.Bilateral ovarian castration surgery was performed in the model group,after successful surgery,hormone withdrawal was performed to establish the postpartum depression model.On the basis of the open field test(OFT)scores,rats were randomly divided into the model group,10μg estradiol group,4.5 mg/kg sertraline group,3.6 g/kg Shenguiren group and 3.6 g/kg Shenguiren+1.2 mg/kg LY294002 group,corresponding drugs were administered for 14 days.The hippocampaus of the rat brain was taken after administration.Hematoxylin-eosin(HE)staining and Nissl staining were used to evaluate the morphology and the number of neurons in rat hippocampal DG.The expressions of Bcl-2,Bax,Bcl-2/Bax ratio and Cleaved-Caspase3 in rat hippocampal tissues were determined by Western Blot(WB).Terminal deoxynucleotidyl transferase-mediated dUTP nice-end labeling(TUNEL)was used to detect the apoptosis of neurons in the DG.Results:Compared with the control group,the number of granulosa cells and Nissl bodies in DG were decreased in the model group(P<0.01),the denaturation or necrosis and other pathological changes were observed,the percentage of cell apoptosis in the hippocampus was significantly increased(P<0.01),the expression level of Bax protein was increased,the Bcl-2/Bax ratio was decreased.After treatment with Shenguiren mixture,no significant pathological changes was observed in the hippocampal DG of the rats(P<0.01).The percentage of apoptosis in the hippocampal tissue was significantly reduced(P<0.01),the expression levels of Bcl-2 and Cleaved-Caspase3 were decreased(P<0.05).Compared with 3.6 g/kg Shenguiren group,the number of granulosa cells and Nissl bodies in DG were significantly decreased i

关 键 词：补虚化瘀法 参归仁合剂 产后抑郁 凋亡 

分 类 号：R285.5[医药卫生—中药学]