妇科千金方对子宫肌瘤模型大鼠激素及其受体的影响及代谢组学研究

Effects of Fuke Qianjin Formula on hormones and their receptors and metabonomics study in uterine fibroids model rats

    摘要
  • 摘要:
    目的探讨妇科千金方（FKQJF）不同部位对子宫肌瘤的作用，确定最佳药效部位。
    方法将FKQJF提取分离得到FKQJF的多糖(FKP)、黄酮(FKF)和油脂(FKG)部位，140只SPF级雌性SD大鼠被分为14组模型组(MOD)，空白组(NC)， 宫瘤清组(GLQ)，米非司酮组(MFST)，FKQJF组，低、中、高剂量多糖组(l-FKP，m-FKP，h-FKP)，低、中、高剂量黄酮组(l-FKF，m-FKF，h-FKF)，低、中、高剂量油脂组(l-FKG，m-FKG，h-FKG)，对子宫肌瘤模型大鼠进行4周的干预。用ELISA试剂盒检测血清中雌激素和孕激素水平；免疫组化法检测雌激素受体α (ER-α)、雌激素受体β (ER-β)和孕激素受体 (PR)；气相质谱法(GC-MS)检测血清代谢物和油脂部位。
    结果FKQJF、h-FKF、m-FKG和h-FKG组子宫肌瘤模型大鼠的雌激素水平显著降低（P < 0.01）；FKQJF、h-FKF和h-FKG组子宫肌瘤模型大鼠孕激素水平显著降低（P < 0.01）。FKQJF和h-FKG组子宫肌瘤模型大鼠ER-α、ER-β和PR水平显著降低（P < 0.01）；m-FKG能降低子宫肌瘤模型大鼠ER-α、ER-β和PR水平（P < 0.05）。血清代谢组学结果也显示h-FKG和FKQJF可调节相关内源性代谢物，使子宫肌瘤大鼠病理指标接近正常组。在油脂中鉴定出46种成分，占油脂部位总成分的91.97%。
    结论FKQJF和h-FKG具有明显的抗子宫肌瘤作用，可明显改善子宫肌瘤模型大鼠的子宫病理状态，其作用原理可能与其可调节子宫肌瘤模型动物的雌孕激素及其受体相关，该研究为FKQJF临床研究和应用提供了实验基础。

     

    Abstract:
    Objective To investigate the effects of different fractions from Fuke Qianjin Formula (妇科千金方, FKQJF) on uterine leiomyoma (UL) to determine the best fraction.
    MethodsFKQJF was extracted and isolated to obtain polysaccharides (FKP), flavonoids (FKF), and grease (FKG). 140 female SPF SD rats were divided into 14 groups model (MOD), normal control (NC), Gouliuqing (GLQ), Mifepristone (MFST), FKQJF, low, medium, and high dose of polysaccharides (l-FKP, m-FKP, and h-FKP), low, medium, and high dose of flavonoids (l-FKF, m-FKF, and h-FKF), low, medium, and high dose of grease (l-FKG, m-FKG, and h-FKG), and uterine fibroids model rats were treated with drugs for four weeks. Serum levels of estrogen and progesterone were measured using enzyme-linked immunoassay assay (ELISA) kits. The expression of estrogen receptor (ER-α, ER-β) and progesterone receptor (PR) in the uterus was observed using immunohistochemistry (IHC). Serum metabolite profiles and FKG were analyzed using gas chromatography-mass spectrometry (GC-MS).
    ResultsFKQJF, h-FKF, m-FKG, and h-FKG significantly downregulated the estrogen level in the uterine fibroid model rats (P < 0.01). FKQJF, h-FKF, and h-FKG significantly reduced the level of progesterone in the uterine fibroid model rats (P < 0.01). The levels of ER-α, ER-β, and PR in uterine fibroid model rats were significantly decreased by FKQJF and h-FKG (P < 0.01). The levels of ER-α, ER-β, and PR in the fibroid model rats were decreased by m-FKG (P < 0.05). Additionally, serum metabolism results revealed that h-FKG and FKQJF could regulate related endogenous metabolites and make the pathological indices of uterine fibroids in rats close to the normal group. Forty-six components were identified in the oil, accounting for 91.97% of the total oil components.
    ConclusionFKQJF and h-FKG showed a significant anti-myoma activity and significantly improved the pathological state of the uterus in rats with hysteromyoma. The mechanism of action may be related to the regulation of estrogen progesterone and its receptor in uterine fibroid model animals. These findings proved the effect of FKQJF on uterine leiomyoma and provided an experimental basis for its clinical research and application.

     

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