毛兰素对多囊卵巢综合征大鼠卵巢颗粒细胞凋亡的影响及机制OA北大核心CSTPCD
Effects of erianin on the apoptosis of ovarian granulosa cells in rats with polycystic ovary syndrome and its mechanism
目的 探究毛兰素(ERI)对多囊卵巢综合征(PCOS)大鼠卵巢颗粒细胞凋亡的影响及机制.方法 通过皮下注射脱氢表雄酮构建PCOS大鼠模型,将造模成功的大鼠随机分为PCOS组,ERI低、中、高剂量组(10、20、40 mg/kg)和ERI高剂量+维替泊芬组(40 mg/kg ERI+10 mg/kg维替泊芬),每组10只;另取10只正常大鼠作为正常组.各给药组大鼠灌胃相应剂量的ERI和/或腹腔注射维替泊芬,PCOS组和正常组大鼠灌胃等体积的1%二甲基亚砜,每日1次,连续6周.给药结束后,检测各组大鼠体重和空腹血糖(FPG),血清中雌二醇(E2)、睾酮(T)、卵泡刺激素(FSH)、黄体生成素(LH)水平,观察卵巢组织形态学变化,分析卵巢组织细胞凋亡情况,检测卵巢组织中凋亡相关蛋白[B细胞淋巴瘤2(Bcl-2)、Bcl-2相关X蛋白(Bax)、胱天蛋白酶3(Caspase-3)]和Hippo-YAP信号通路相关蛋白[大肿瘤抑制激酶1(LATS1)、磷酸化LATS1(p-LATS1)、Yes相关蛋白(YAP)、磷酸化YAP(p-YAP)、转录共激活子因子PDZ结合基序(TAZ)]表达水平.结果 与PCOS组比较,ERI低、中、高剂量组大鼠卵巢多囊特征减轻,闭锁卵泡数量减少,颗粒细胞层增厚,体重、FPG水平、T水平、LH水平、LH/FSH、囊性卵泡数量、细胞凋亡指数和Bax、Caspase-3、p-LATS1、p-YAP蛋白表达水平均显著降低或减少(P＜0.05),黄体数量、E2水平和Bcl-2、LATS1、YAP、TAZ蛋白表达水平均显著升高或增多(P＜0.05).与ERI高剂量组比较,ERI高剂量+维替泊芬组大鼠的上述指标变化均被抑制(P＜0.05).结论 ERI能促进PCOS大鼠卵巢颗粒细胞增殖,调节性激素水平,其作用机制可能与抑制Hippo-YAP信号通路有关.
OBJECTIVE To investigate the effects of erianin(ERI)on the apoptosis of ovarian granulosa cells in rats with polycystic ovary syndrome(PCOS)and its mechanism.METHODS PCOS rat model was constructed by subcutaneous injection of dehydroepiandrosterone,and the successfully constructed rats were randomly divided into PCOS group,ERI low-dose,medium-dose and high-dose groups(10,20,40 mg/kg)and ERI high dose+verteporfin group(40 mg/kg ERI+10 mg/kg verteporfin),with 10 rats in each group.Another 10 normal rats were selected as the normal group.Rats in each administration group were given corresponding dose of ERI and/or intraperitoneal injection of vitiporfin,and rats in the PCOS group and normal group were orally administered an equal volume of 1%dimethyl sulfoxide,once a day,for 6 consecutive weeks.After administration,the body weight,fasting blood glucose(FPG),serum levels of estradiol(E2),testosterone(T),follicle stimulating hormone(FSH)and luteinizing hormone(LH)were detected in each group;morphological changes in ovarian tissue were observed,and the apoptosis of ovarian tissue cells was analyzed.Apoptosis-associated proteins[B-cell lymphoma-2(Bcl-2),Bcl-2 associated X protein(Bax),Caspase-3]and Hippo-YAP signaling pathway associated proteins[large tumor suppressor kinase 1(LATS1),phosphorylated LATS1(p-LATS1)and Yes associated protein(YAP),phosphorylated YAP(p-YAP),transcriptional co-activator with PDZ binding motif(TAZ)]were detected in ovarian tissue.RESULTS Compared with PCOS group,the ovarian polycystic characteristics of the ERI low-dose,medium-dose,and high-dose groups were reduced,the number of atretic follicles was reduced,and the granulosa cell layer was thickened;the body mass,FPG,T,LH,LH/FSH,the number of cystic follicles,cell apoptosis index,protein expressions of Bax,Caspase-3,p-LATS1 and p-YAP were greatly decreased(P＜0.05);the number of corpus luteum,protein expressions of E2,Bcl-2,LATS1,YAP and TAZ were greatly increased(P＜0.05).Compared with ERI high-dose group,the above indexes in ERI high-dose+vitiporfin group were inhibited(P＜0.05).CONCLUSIONS ERI can promote the proliferation of ovarian granulosa cells and improve the level of sex hormones in PCOS rats,and its mechanism of action may be related to the inhibition of the Hippo-YAP signaling pathway.
房丽娜;李妍仪;董超;许丽丽;史兆松;李越东;杨波;许再超
承德市中心医院生殖医学科,河北 承德 067000
药学
毛兰素颗粒细胞多囊卵巢综合征Hippo-YAP信号通路卵巢功能性激素
erianingranulosa cellpolycystic ovary syndromeHippo-YAP signaling pathwayovarian functionsex hormone
《中国药房》 2024 (011)
1339-1344 / 6
河北省医学科学研究课题(No.20241284);承德市科技计划自筹经费项目(No.202204A006)
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