文献类型：期刊文献

中文题名：基于HIF-1α/VEGF信号通路探讨敦煌疗风虚瘦弱方拮抗PCOS卵巢纤维化的作用机制

英文题名：Exploring the mechanism of Dunhuangliao Fengxu Shouruo Formula(敦煌疗风虚瘦弱方)in antagonizing ovarian fibrosis of PCOS rats based on the HIF-1α/VEGF signaling pathway

作者：张小花[1];李鹤[1];芮守月[1];蔺文娟[1];黄灿灿[1];李善政[2];袁荣荣[1];万文文[1];张舒媛[1];林祥羽[1];毛海燕[3];张志瑞[1];武权生[1]

第一作者：张小花

机构：[1]甘肃中医药大学,甘肃兰州730000;[2]河南中医药大学,河南郑州450046;[3]甘肃省人民医院,甘肃兰州730050

第一机构：甘肃中医药大学

年份：2025

卷号：36

期号：7

起止页码：1225

中文期刊名：时珍国医国药

外文期刊名：Lishizhen Medicine and Materia Medica Research

收录：;北大核心:【北大核心2023】；

基金：国家自然科学基金项目(82260949);甘肃省教育厅创新基金项目(2022A-065);甘肃省中医药管理局科研课题(GZKP-2023-44)。

语种：中文

中文关键词：多囊卵巢综合征;HIF-1α/VEGF信号通路;敦煌疗风虚瘦弱方;卵巢纤维化

外文关键词：Polycystic ovary syndrome;HIF-1α/VEGF signaling pathway;Dunhuangliao Fengxu Shouruo Formula(敦煌疗风虚瘦弱方);Ovarian fibrosis

摘要：目的 基于缺氧诱导因子-1α/血管内皮生长因子(HIF-1α/VEGF)通路观察敦煌疗风虚瘦弱方对来曲唑诱导的PCOS模型大鼠卵巢纤维化的治疗作用。方法 48只雌性SD大鼠随机分组,采用来曲唑建立PCOS卵巢纤维化模型,优思悦组给予0.01g·kg^(-1)·d^(-1)屈螺酮炔雌醇片灌胃,中药低、中、高剂量组分别给予3.10,6.21,12.42g·kg^(-1)敦煌疗风虚瘦弱方灌胃,连续28d。阴道涂片动态监测大鼠动情周期,采用HE染色观察卵巢组织病理学形态改变,ELISA检测大鼠血清FSH、LH、T、E_(2)的水平,通过RT-qPCR、IHC测定卵巢组织中HIF-1α/VEGF信号通路mRNA及蛋白表达,Western blot检测卵巢组织中HIF-1α/VEGF信号通路及TGF-β1、α-SMA、E-cad纤维化相关蛋白的表达水平。结果 与空白组相比,模型组大鼠体质量增加,LH、T水平及LH/FSH比值上升(P<0.01),E_(2)水平下降(P<0.05)。卵巢组织中HIF-1α、VEGF mRNA表达升高(P<0.01),HIF-1α、VEGF、TGF-β1、α-SMA的蛋白水平增加,E-cad表达降低(P<0.01)。优思悦组和敦煌疗风虚瘦弱方组大鼠卵巢组织中HIF-1α、VEGF mRNA表达降低(P<0.01,P<0.05),蛋白水平的HIF-1α、VEGF、TGF-β1、α-SMA下降,E-cad增加(P<0.01,P<0.05),特别是高剂量组效果更显著。结论 敦煌疗风虚瘦弱方可以改善来曲唑诱导的PCOS大鼠的一般情况、性激素水平及卵巢纤维化表现,其治疗机制可能与HIF-1α/VEGF信号通路的调节有关。
Objective To investigate the therapeutic effect of the Dunhuangliao Fengxu Shouruo Formula(敦煌疗风虚瘦弱方, DFSF) on ovarian fibrosis in the letrozole-induced polycystic ovary syndrome(PCOS) model rats, based on the hypoxia-inducible factor-1α/vascular endothelial growth factor(HIF-1α/VEGF) pathway. Methods Forty-eight female SD rats were randomly divided into different groups. A PCOS ovarian fibrosis model was established using letrozole. The Yousiyue group(优思悦组) received 0.01 g·kg^(-1)·d^(-1) of drospirenone and ethinylestradiol tablets via gavage, while the low/medium/high-dose DFSF groups received 3.10, 6.21, and 12.42 g·kg^(-1) of DFSF respectively, for 28 consecutive days. Vaginal smears were used to dynamically monitor the estrous cycle. Hematoxylin-eosin(HE) staining was employed to observe ovarian histopathological changes. Serum levels of follicle-stimulating hormone(FSH), luteinizing hormone(LH), testosterone(T), and estradiol(E_(2)) were measured using ELISA. RT-qPCR and immunohistochemistry(IHC) were used to assess mRNA and protein expression of the HIF-1α/VEGF pathway in the ovarian tissues. Western blot(WB) was performed to detect protein level of the HIF-1α/VEGF pathway and fibrosis-related markers of TGF-β1, α-SMA, and E-cad. Results Compared with the blank group, the model group showed increased body weight, elevated LH, T levels, and LH/FSH ratio(P<0.01), and reduced E_(2) level(P<0.05). Ovarian tissues exhibited up-regulated mRNA expressions of HIF-1α and VEGF(P<0.01), increased protein levels of HIF-1α, VEGF, TGF-β1, and α-SMA, and decreased E-cad expression(P<0.01). Both the Yousiyue group and all dose DFSF groups demonstrated reduced mRNA expressions of HIF-1α and VEGF(P<0.01, P<0.05), decreased protein levels of HIF-1α, VEGF, TGF-β1, and α-SMA, and increased E-cad(P<0.01, P<0.05), with the high-dose DFSF group showing the most significant effects. Conclusion DFSF ameliorates general conditions, sex hormone levels, and ovarian fibrosis in letrozole-induced PCOS rats. Its therapeutic mechanism may be associated with the regulation of the HIF-1α/VEGF signaling pathway.