北京中医药大学学报2026，Vol.49Issue(5)：642-654,13.DOI:10.3969/j.issn.1006-2157.2026.05.007
补肾调经方调控白血病抑制因子及其受体对高龄小鼠卵巢颗粒细胞增殖与类固醇激素分泌的影响
Bushen Tiaojing Formula on ovarian granulosa cell proliferation and steroid hormone secretion in aged mice by regulating LIF and its receptor
摘要
Abstract
Objective To explore the mechanism of Bushen Tiaojing Formula(BSTJF)underlying the promotion of proliferation and steroid hormone synthesis of ovarian granulosa cells in aged mice.Methods Twenty 7-8-week-old ICR female mice were assigned to the control group(intragastric administration of distilled water),and eighty 9-10-month-old ICR female mice were equally divided into the model group(intragastric administration of distilled water),the BSTJF low-dose group(intragastric administration of 25.6 g/kg BSTJF),the BSTJF high-dose group(intragastric administration of 51.2g/kg BSTJF),and the leukemia inhibitory factor(LIF)inhibitor group was treated with intragastric administration of BSTJF(51.2g/kg)and intraperitoneal injection of EC330(5.0×10-4 g/kg)according to random numbers.All groups underwent daily gavage or intraperitoneal administration for 30 days.The estrous cycle changes of mice were observed by a vaginal exfoliated cell smear.The levels of sex hormones were detected by ELISA.The mRNA and protein expressions of proliferating cell nuclear antigen(PCNA),the cell cycle protein D1(Cyclin D1),the acute steroidogenic regulatory protein(StAR),3β-hydroxysteroid dehydrogenase(3β-HSD),cytochrome P450 19A1(CYP19A1),LIF,and LIF receptor(LIFR)were detected by quantitative reverse transcription PCR and Western blotting.The expressions of LIF and LIFR were detected by immunohistochemistry.Results Compared with the control group,the estrous cycles of the mice in the model group were disordered and prolonged(P<0.05),the levels of estradiol(E2)and progesterone(P4)decreased(P<0.05),the levels of follicle stimulating hormone(FSH),luteinizing hormone(LH),and the FSH/LH ratio increased(P<0.05).The mRNA and protein expressions of PCNA,Cyclin D1,StAR,3β-HSD,CYP19A1,LIF,and LIFR in granulosa cells decreased(P<0.05).Compared with the model group,the estrous cycles of the low-and high-dose groups of BSTJF were more regular and shorter(P<0.05),the levels of E2 and P4 increased(P<0.05),the levels of FSH,LH,and FSH/LH ratio decreased(P<0.05),and the mRNA and protein expressions of PCNA,Cyclin D1,StAR,3β-HSD,CYP19A1,LIF and LIFR in granulosa cells increased(P<0.05).Compared with the BSTJF high-dose group,the estrous cycle of mice in the LIF inhibitor group was disordered and prolonged(P<0.05),the levels of E2 and P4 decreased(P<0.05),FSH and LH levels increased as did the FSH/LH ratio(P<0.05).In addition,the mRNA and protein expressions of PCNA,Cyclin D1,StAR,3β-HSD,CYP19A1,and LIFR in granulosa cells decreased(P<0.05).Conclusion BSTJF may improve ovarian reserve function and promote follicular development by up-regulating LIF and LIFR,mediating the proliferation and steroid hormones synthesis of granulosa cells.关键词
补肾调经方/白血病抑制因子/颗粒细胞/类固醇激素/小鼠Key words
Bushen Tiaojing Formula/leukemia inhibitory factor/granulosa cells/steroid hormone/mice分类
医药卫生引用本文复制引用
李昆,张拴成,孙莹,宋亚静,集川原,熊文艳,杜惠兰,马玉聪..补肾调经方调控白血病抑制因子及其受体对高龄小鼠卵巢颗粒细胞增殖与类固醇激素分泌的影响[J].北京中医药大学学报,2026,49(5):642-654,13.基金项目
国家自然科学基金项目(No.82405455) （No.82405455）
河北省自然科学基金项目(No.H2022423331) （No.H2022423331）
河北省中医药管理局科研计划项目(No.2023122,2023124) （No.2023122,2023124）
河北省高等学校科学技术研究项目(No.QN2024039) （No.QN2024039）
河北省属高校基本科研业务费专项(No.TDZR2024001). National Natural Science Foundation of China(No.82405455) （No.TDZR2024001）
