中国实验方剂学杂志2026，Vol.32Issue(7)：46-55,10.DOI:10.13422/j.cnki.syfjx.20252107
养精种玉汤调控SIRT1/PGC-1α信号通路改善卵巢储备功能减退大鼠线粒体功能及氧化应激损伤的机制
Mechanism of Yangjing Zhongyutang in Regulating SIRT1/PGC-1α Signaling Pathway to Promote Mitochondrial Function and Alleviate Oxidative Stress Damage in Rats with Diminished Ovarian Reserve
摘要
Abstract
Objective:To observe the effects of Yangjing Zhongyutang(YJZYT)on mitochondrial biogenesis and oxidative stress damage mediated by the silent information regulator 1(SIRT1)/peroxisome proliferator-activated receptor gamma coactivator-1 alpha(PGC-1α)signaling pathway in cyclophosphamide(CTX)-induced rats with diminished ovarian reserve(DOR),and to explore its mechanism in improving ovarian reserve function and follicular development.Methods:Forty-two 8-week-old female SD rats with normal estrous cycles were randomly divided into a blank control group(n=7)and a model group(n=35).Rats in the model group received a single intraperitoneal injection of CTX(90 mg·kg-1)to establish the DOR model.After modeling,estrous cycles were monitored for 7 consecutive days,and model success was confirmed based on criteria for estrous cycle disruption.After successful modeling,rats were divided into groups for intervention:estradiol valerate group(0.09 mg·kg-1),and YJZYT high-,medium-,and low-dose groups(19.98,9.99,5.00 g·kg-1).The blank control group and model group were given an equal volume of distilled water by gavage.All groups received daily gavage once for 4 consecutive weeks.The general state,body weight,and ovarian wet weight of rats were observed and recorded,and the ovarian organ index was calculated.Enzyme-linked immunosorbent assay(ELISA)was used to measure serum levels of follicle-stimulating hormone(FSH),luteinizing hormone(LH),estradiol(E2),anti-Müllerian hormone(AMH),superoxide dismutase(SOD),and glutathione peroxidase(GSH-Px).Hematoxylin-eosin(HE)staining was performed to observe ovarian histomorphological changes and follicular development status.Immunofluorescence was used to detect reactive oxygen species(ROS)expression levels.Colorimetric assays were employed to measure adenosine triphosphate(ATP)and malondialdehyde(MDA)content in ovarian tissues.Quantitative Real-time polymerase chain reaction(Real-time PCR)was used to detect mitochondrial DNA(mtDNA)copy number and the mRNA expression levels of key genes including SIRT1,PGC-1α,nuclear respiratory factor 1(NRF1),and mitochondrial transcription factor A(TFAM).Western blot was performed to detect the protein expression levels of SIRT1,PGC-1α,NRF1,and TFAM.Results:Compared with the blank group,rats in the model group exhibited disrupted estrous cycles,obviously reduced body weight,and decreased ovarian index(P＜0.05).Ovarian histopathology revealed cortical thinning,loose structure,and a significant reduction in both primordial and growing follicles(P＜0.01).Serum FSH and LH levels were significantly elevated(P＜0.01),while E2 and AMH levels were obviously reduced(P＜0.05,P＜0.01).ATP content and mtDNA copy number decreased in ovarian tissue(P＜0.01),ROS expression increased,MDA levels rose,while SOD and GSH-Px activities obviously decreased(P＜0.05,P＜0.01),mRNA and protein expression levels of SIRT1,PGC-1α,NRF1,and TFAM were obviously downregulated(P＜0.05,P＜0.01).After treatment,compared with the model group,body weight and ovarian index obviously recovered in rats administered various doses of YJZYT(P＜0.05),serum E2 and AMH levels increased,while FSH and LH levels obviously decreased(P＜0.05,P＜0.01),ovarian tissue ATP content and mtDNA copy number were up-regulated,ROS and MDA levels decreased,and antioxidant enzymes SOD and GSH-Px activity obviously increased(P＜0.05,P＜0.01),Gene and protein expression levels related to the SIRT1/PGC-1α/NRF1/TFAM signaling pathway were obviously up-regulated compared to the model group(P＜0.05,P＜0.01),HE staining revealed that ovarian structure gradually recovered to integrity in all treatment groups,with a obviously increase in the number of primordial and growing follicles(P＜0.05,P＜0.01).Granulosa cells were neatly arranged,indicating marked improvement in ovarian function.Conclusion:YJZYT may improve ovarian function and follicular development in rats with diminished ovarian reserve by activating the SIRT1/PGC-1α signaling pathway,promoting mitochondrial biogenesis,enhancing mitochondrial function,and alleviating oxidative stress damage.关键词
养精种玉汤/卵巢储备功能减退/沉默信息调节因子1(SIRT1)/过氧化物酶体增殖物激活受体γ共激活因子-1α(PGC-1α)信号通路/氧化应激/线粒体Key words
Yangjing Zhongyutang/diminished ovarian reserve(DOR)/silent information regulator 1(SIRT1)/peroxisome proliferator-activated receptor gamma coactivator-1alpha(PGC-1α)signaling pathway/oxidative stress/mitochondria分类
医药卫生引用本文复制引用
张萍,杨丽娟,陈胜辉,姚文亮,周玉良,马玲,吴慧颖,徐燕文,周紫嫣..养精种玉汤调控SIRT1/PGC-1α信号通路改善卵巢储备功能减退大鼠线粒体功能及氧化应激损伤的机制[J].中国实验方剂学杂志,2026,32(7):46-55,10.基金项目
江西省中医药管理局科技计划项目(2024B0581) （2024B0581）
