[1]唐 密,彭艳丽,罗 岚.补肾活血方调控IGFBP4/IGFs信号通路改善肥胖不孕小鼠卵巢功能异常的机制[J].陕西中医,2025,46(5):600-605.[doi:DOI:10.3969/j.issn.1000-7369.2025.05.005]
　TANG Mi,PENG Yanli,LUO Lan.The mechanism by which the Bushen Huoxue formula regulates the IGFBP4/IGFs signaling pathway to improve ovarian dysfunction in obese infertile mice[J].,2025,46(5):600-605.[doi:DOI:10.3969/j.issn.1000-7369.2025.05.005]
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补肾活血方调控IGFBP4/IGFs信号通路改善肥胖不孕小鼠卵巢功能异常的机制
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《陕西中医》[ISSN:1000-7369/CN:61-1281/TN]

卷:
46
期数:
2025年5期
页码:
600-605
栏目:
基础研究
出版日期:
2025-05-05

文章信息/Info

Title:
The mechanism by which the Bushen Huoxue formula regulates the IGFBP4/IGFs signaling pathway to improve ovarian dysfunction in obese infertile mice
作者:
唐 密; 彭艳丽; 罗 岚
(湖南省妇幼保健院中医妇科,湖南 长沙 410008)
Author(s):
TANG Mi; PENG Yanli; LUO Lan
(Hunan Maternal and Child Health Hospital,Gynecology of Traditional Chinese Medicine,Changsha 410008,China)
关键词:
肥胖;  不孕;  补肾活血方;  IGFBP4/IGFs 信号通路;  卵巢功能
Keywords:
Obesity;  Infertility;  Bushen Huoxue formula;  IGFBP4/IGFs signaling pathway;  Ovarian function
分类号:
R 271.14
DOI:
DOI:10.3969/j.issn.1000-7369.2025.05.005
文献标志码:
A
摘要:
目的:探究补肾活血方调控IGFBP4/IGFs信号通路以改善肥胖不孕小鼠卵巢功能异常的机制。方法:通过体外培养人卵巢颗粒细胞,设置对照组、高脂组、补肾活血方组进行对比实验。通过建立肥胖不孕小鼠模型,分为正常对照组、肥胖不孕模型组、补肾活血方低、高剂量组,每组 10 只。全面检测细胞活性、激素分泌水平、IGFBP4/IGFs信号通路相关蛋白和mRNA表达等指标; 同时,对小鼠进行卵巢功能指标检测、性激素水平检测、IGFBP4/IGFs信号通路相关蛋白和mRNA表达检测以及卵巢组织病理学检查。结果:与对照组相比,高脂组细胞活性显著降低,补肾活血方组能有效提高细胞活性(P<0.05)。高脂组 E2 和 P 分泌水平明显下降,补肾活血方组则能促使其分泌水平回升(P < 0.05)。高脂组IGFBP4蛋白和mRNA表达水平升高,IGF-1胰岛素样生长因子1(IGF-1)、胰岛素样生长因子1受体(IGF-1R)、胰岛素受体底物(1IRS-1)、蛋白激酶B(Akt)、哺乳动物雷帕霉素靶蛋白(mTOR)蛋白和mRNA表达水平降低; 补肾活血方组能使IGFBP4表达降低,IGF-1、IGF-1R、IRS-1、Akt、mTOR蛋白和mRNA表达升高(P< 0.05,P<0.01,P<0.001)。在小鼠实验中,肥胖不孕模型组体重增长迅速,卵巢重量、卵泡和黄体数量减少,血清中E2、P水平降低,卵巢组织中IGFBP4蛋白和 mRNA 表达升高,IGF-1、IGF-1R、IRS-1、Akt、mTOR 蛋白和mRNA表达降低; 补肾活血方低剂量组和高剂量组能改善这些指标,且高剂量组效果更为显著(P<0.05,P<0.01)。结论:补肾活血方可能通过调控IGFBP4/IGFs信号通路来改善肥胖不孕小鼠的卵巢功能异常,为临床治疗肥胖不孕患者提供了新的科学依据和治疗思路。
Abstract:
Objective:This experiment aims to explore the mechanism by which the Bushen Huoxue formula regulates the IGFBP4/IGFs signaling pathway to improve ovarian dysfunction in obese infertile mice.Methods:Human ovarian granulosa cells were cultured in vitro. The cells were divided into a normal control group, a high-fat group, and a Bushen Huoxue formula group for comparative experiments.An obese infertile mouse model was established,The mice were divided into 4 groups,the normal control group,the obese infertile model group,the low-dose and high-dose Bushen Huoxue formula groups,10 rats in each group.A comprehensive examination of cell viability,hormone secretion levels,IGFBP4/IGFs signaling pathway-related protein and mRNA expression,and ovarian function indicators,sex hormone levels,IGFBP4/IGFs signaling pathway-related protein and mRNA expression,and ovarian histopathology in mice were conducted.Results:Compared with the control group,the cell viability in the obese inferyile model group was significantly reduced,while the Bushen Huoxue formula group could effectively increase cell viability(P<0.05).The secretion levels of E2 and P in the high-fat group decreased significantly, while the Bushen Huoxue formula group could promote the recovery of these secretion levels(P < 0.05).In addition,the expression levels of IGFBP4 protein and mRNA in the obese inferyile model group increased,while the expression levels of IGF-1,IGF-1R,IRS-1,Akt,mTOR protein,and mRNA decreased. The Bushen Huoxue formula group could reverse these changes,reducing the expression of IGFBP4 and increasing the expression of IGF-1,IGF-1R,IRS-1,Akt,mTOR protein,and mRNA(P<0.05,P<0.01,P<0.001).In the mouse experiment,the obese infertile model group showed rapid weight gain,reduced ovarian weight,decreased numbers of follicles and corpora lutea,decreased levels of E2 and P in the serum,increased expression of IGFBP4 protein and mRNA in the ovarian tissue,and decreased expression of IGF-1,IGF-1R,IRS-1,Akt,mTOR protein,and mRNA.The low-dose and high-dose Bushen Huoxue formula groups could improve these indicators,and the high-dose group had a more significant effect(P<0.05,P<0.01).Conclusion:The Bushen Huoxue formula may improve ovarian dysfunction in obese infertile mice by regulating the IGFBP4/IGFs signaling pathway,providing a new scientific basis and therapeutic approach for the clinical treatment of obesity-related infertility.

参考文献/References:

[1] SZMYGIN H,SZMYGIN M,CHEDA M,et al.Current insights into the potential role of fMRI in discovering the mechanisms underlying obesity[J].Journal of Clinical Medicine,2023,12(13):4379.
[2] TANG J,XU Y,WANG Z,et al.Association between metabolic healthy obesity and female infertility:The national health and nutrition examination survey,2013-2020[J].BMC Public Health,2023,23(1):1524.
[3] ENNAB F,ATIOMO W.Obesity and female infertility[J].Best Practice & Research Clinical Obstetrics & Gynaecology,2023,89:102336.
[4] PARFENTEVA O I,KULEMIN N A,BONDAREVA E A,et al.Prevalence and predictors of normal-weight Obesity among women[J].Nutrients,2024,16(16):2579.
[5] AVELLAR A P,DE SOUZA PEREIRA A C,REQUEIJO M J R.A relacao entre a obesidadeea infertilidade:Uma revisao de literatura[J].Research,Society and Development,2023,12(8):e0312842803.
[6] 程春秀,魏玉业,李玲,等.坤泰胶囊联合二甲双胍治疗超重或肥胖PCOS不孕症患者的临床效果[J].中国性科学,2025,34(1):134-138.
[7] FLETCHER E J,SANTACRUZ-MARQUEZ R,MOURIKES V E,et al.Effects of phthalate mixtures on ovarian folliculogenesis and steroidogenesis[J].Toxics,2022,10(5):251.
[8] NOURI N,SHAREGHI-OSKOUE O,AGHEBATI-MALEKI L,et al.Role of miRNAs interference on ovarian functions and premature ovarian failure[J].Cell Communication and Signaling,2022,20(1):198.
[9] SHEIKH S,LO B K,KAUNE H,et al.Rescue of follicle development after oocyte-induced ovary dysfunction and infertility in a model of POI[J].Frontiers in Cell and Developmental Biology,2023,11:1202411.
[10] DING T,WANG T,ZHANG J,et al.Analysis of ovarian injury associated with COVID-19 disease in reproductive-aged women in Wuhan,China:An observational study [J].Frontiers in Medicine,2021,8:635255.
[11] PIAU T B,DE QUEIROZ RODRIGUES A,PAULINI F.Insulin-like growth factor(IGF)performance in ovarian function and applications in reproductive biotechnologies[J].Growth Hormone & IGF Research,2023:101561.
[12] LI X,LIN S,YANG X,et al.When IGF-1 meets metabolic inflammation and polycystic ovary syndrome[J].International Immunopharmacology,2024,138:112529.
[13] CHEN X,SHAO C,LIU J,et al.ULK2 suppresses ovarian cancer cell migration and invasion by elevating IGFBP3[J].Peer J,2024,12:e17628.
[14] LEROITH D,HOLLY J M,FORBES B E.Insulin-like growth factors:Ligands,binding proteins,and receptors[J].Molecular Metabolism,2021,52:101245.
[15] WATERS J A,URBANO I,ROBINSON M,et al.Insulin-like growth factor binding protein 5:Diverse roles in cancer[J].Frontiers in Oncology,2022,12:1052457.
[16] AFRADIASBAGHARANI P,HOSSEINI E,ALLAHVEISI A,et al.The insulin-like growth factor and its players:Their functions,significance,and consequences in all aspects of ovarian physiology[J].Middle East Fertility Society Journal,2022,27(1):27.
[17] LIAO L,TAO P,XU Q,et al.Bushen Huoxue formula protects against renal fibrosis and pyroptosis in chronic kidney disease by inhibiting ROS/NLRP3-mediated inflammasome activation[J].Renal Failure,2024,46(1):2354444.
[18] HUANG Y,HU R,LIU Z,et al.Bushen Huoxue recipe ameliorates ovarian function via promoting BMSCs proliferation and homing to ovaries in POI mice[J].Phytomedicine,2024,129:155630.
[19] LI J,ZHU H,ZHU Y,et al.Effect of Bushen Huoxue recipe on serum metabolomics in polycystic ovary syndrome rats[J].Gynecological Endocrinology,2023,39(1):2260500.
[20] CHEN S,LU Y,CHEN Y,et al.The effect of Bu Shen Huo Xue Tang on autoimmune premature ovarian insufficiency via Modulation of the Nrf2/Keap1 signaling pathway in mice[J].Journal of Ethnopharmacology,2021,273:113996.
[21] 高扬,朱艳.子宫内膜异位症合并不孕患者血清中基质金属蛋白酶-9、基质金属蛋白酶抑制剂-1、血管内皮生长因子可溶性受体、胰岛素生长因子-1、单核细胞趋化蛋白-1表达水平及临床意义[J].陕西医学杂志,2020,49(4):462-465,501.
[22] 李晖.胰岛素样生长因子-1与胰岛素样生长因子结合蛋白-1在妇产科临床应用的研究进展[J].陕西医学杂志,2004,33(2):153-155.
[23] 闫晓彤,朱婷,章晓乐,等.补肾活血方联合补佳乐对宫腔粘连大鼠YAP1/TGF-β1信号通路的影响[J].陕西中医,2022,43(8):987-991.
[24] 王晓静.补肾活血方联合达英-35治疗多囊卵巢综合征临床研究[J].陕西中医,2018,39(7):842-844.
[25] 李潇,周艳艳.补肾活血方对肾虚血瘀型子宫内膜异位症不孕患者子宫内膜容受性的影响[J].陕西中医,2018,39(3):341-344.

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备注/Memo

备注/Memo:
[基金项目]湖南省卫生健康委员会科研计划项目(D202304153146)
更新日期/Last Update: 2025-05-08