淫羊藿苷基于GDF-9/Smads对多囊卵巢小鼠排卵的作用  

Effect of icariin on ovulatory dysfunctional in polycystic ovary mice through GDF-9/Smads

作　　者：王小洁 张云锋 张彦敏 WANG Xiaojie;ZHANG Yunfeng;ZHANG Yanmin(Department of Gynecology of Traditional Chinese Medicine(TCM),Handan Maternal and Children Health Hospital,Handan 056000,China;TCM Expert Clinic of Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine,Cangzhou 061000,China;Department of Internal Medicine,People s Hospital of Jingxing Mining Area,Shijiazhuang 050100,China)

机构地区：[1]邯郸市妇幼保健院中医妇科,邯郸056000 [2]河北省沧州中西医结合医院中医专家门诊,沧州061000 [3]石家庄市井陉矿区人民医院内科,石家庄050100

出　　处：《西北药学杂志》2023年第5期65-70,共6页Northwest Pharmaceutical Journal

基　　金：2022年度河北省中医药类科研计划课题项目(编号:2022602)。

摘　　要：目的探讨淫羊藿苷(icariin,ICA)对多囊卵巢综合征(polycystic ovarian syndrome,PCOS)小鼠排卵障碍和卵泡发育的作用。方法取50只小鼠,40只用脱氢表雄酮法建立PCOS模型,随机分为模型组及ICA低剂量、中剂量和高剂量组,每组10只,剩余10只未建立模型的小鼠作为对照组。ICA低剂量、中剂量和高剂量组分别按25、50、75 mg·kg^(-1)腹腔注射0.5 mL ICA(溶于9 g·L^(-1)氯化钠注射液0.5 mL中),对照组和模型组腹腔注射9 g·L^(-1)氯化钠注射液,比较各组小鼠激素水平、脏器指数、卵巢形态学差异、卵母细胞凋亡率、生长分化因子9(growth differentiation factor-9,GDF-9)、骨形成蛋白Ⅱ型受体(bone morphogenetic protein typeⅡreceptor,BMPR-Ⅱ)、激活素受体样激酶5(activin receptor like kinase 5,ALK5)、磷酸化Smad蛋白2(phospho-Smad protein 2,p-Smad2)及p-Smad3蛋白水平的差异。结果HE结果显示ICA各剂量组小鼠各级卵泡数量增多,颗粒细胞层数增加、囊性卵泡数量减少;ICA各剂量组睾酮激素(testosterone,T)、促黄体生成激素(luteinizinghor mone,LH)、抗缪勒管激素(anti-Müllerian hormone,AMH)水平、卵巢指数、囊性卵泡数量以及卵泡细胞凋亡率较模型组降低,卵泡刺激素(follicle stimulating hormone,FSH)、雌二醇(estradiol,E 2)水平、子宫指数、生长卵泡数量、黄体数量、GDF-9、BMPR-Ⅱ、ALK5、p-Smad2、p-Smad3蛋白表达水平较模型组升高(P<0.05);T、LH、AMH水平及卵巢指数、囊性卵泡数量、卵泡细胞凋亡率与ICA呈剂量依赖性降低,E 2、FSH水平、子宫指数、生长卵泡数量、黄体数量以及GDF-9、BMPR-Ⅱ、ALK5、p-Smad2和p-Smad3蛋白的表达水平与ICA呈剂量依赖性升高(P<0.05)。结论ICA能有效调节PCOS小鼠生殖激素水平,改善内分泌代谢,促进卵泡发育、成熟,减少卵泡凋亡,改善排卵,可能与调控GDF-9/Smads信号通路蛋白的表达有关。Objective To investigate the effects of icariin(ICA)on ovulation disorder and follicular development in polycystic ovary syndrome(PCOS)mice.Methods 50 mice were taken and 40 were used to establish PCOS model by dehydroepiandrosterone method,which were randomly divided into model group,ICA low,medium and high dose groups,with 10 mice in each group,and the remaining 10 mice without model were used as control group.The low,medium and high dose groups of ICA were intra-peritoneally injected with 0.5 mL of 25,50 and 75 mg·kg^(-1) ICA(dissolved in 9 g·L^(-1)Sodium Chloride Injections),and 9 g·L^(-1)Sodium Chloride Injections were intraperitoneally injected into the control group and the model group.The levels of hormone,organ index,ovarian morphology,oocyte apoptosis,growth differentiation factor-9(GDF-9),bone morphogenetic protein type II receptor(BMPR-Ⅱ),activin receptor like kinase 5(ALK5),phospho-Smad protein 2(p-smad2)and p-Smad 3 were compared.Results The HE staining results showed that the number of follicles and the number of granular cell layers increased,the number of cystic follicles decreased in different dose group of ICA.The levels of testosterone(T),luteinizinghor mone(LH),anti-Müllerian hormone(AMH),ovarian index,number of cystic follicles and follicular cell apoptosis in ICA different groups were lower than those in model group,while the levels of estradiol(E 2),follicle stimulating hormone(FSH),uterine index,number of growing follicles,number of corpus luteum and the expression levels of GDF-9,BMPR-Ⅱ,ALK5,p-Smad2 and p-Smad3 protein were higher than those in model group(P<0.05).The levels of T,LH,AMH,ovarian index,the number of cystic follicles and follicular cell apoptosis decreased in a dose-dependent manner with ICA,while the levels of E 2,FSH,uterine index,the number of growing follicles,the number of corpus luteum,and the expression levels of GDF-9,BMPR-Ⅱ,ALK5,p-Smad2 and p-Smad3 increased in a dose-dependent manner with ICA(P<0.05).Conclusion ICA can effectively regulate the level of r

关 键 词：淫羊藿苷 多囊卵巢综合征 排卵障碍 卵泡发育 生长分化因子9/Smad蛋白家族 

分 类 号：R965[医药卫生—药理学]