Tang Bi-Xin, Meng Qing-Yi, Xie Chan, Zhao Shen-Shen, Wu Kun-Lun, Wang Fang, Du Le-Yi
Department of Traditional Chinese Medicine, Gongli Hospital of Shanghai Pudong New Area, Shanghai 200135, China.
School of Traditional Chinese Medicine, Ningxia Medical University, Yinchuan 750004, China.
Evid Based Complement Alternat Med. 2020 Nov 7;2020:8895809. doi: 10.1155/2020/8895809. eCollection 2020.
Perimenopausal syndrome (PMS) has a high incidence rate and affects the physical and mental health of middle-aged and elderly women. The blockage of PMS is significant in improving the health of perimenopausal women. Currently, for PMS prevention and treatment, traditional Chinese medicine (TCM) has become an ideal choice because of its safety and effectiveness. This study aimed to explore the anti-PMS effects of Ziyin Bushen Decoction (DKTP) and the underlying mechanism. Thirty female Wistar rats were divided into 5 groups ( = 6): control group, low-dose DKTP group, medium-dose DKTP group, high-dose DKTP group, and nilestriol group. The estradiol (E2) level in rat peripheral blood was analyzed using an E2 Radioimmunoassay Kit, and uterine morphologic changes were examined by hematoxylin-eosin staining. Learning and memory ability of rats was assessed by Morris water maze (MWM) and novel object recognition (NOR) task. E2 synthesis, metabolism, and transport associated estrogen receptor-alpha (ER), GnRHR, CYP17, CYP11A1, CYP19, 17HSD, STS, and SHGB were assessed to explore the E2-promoting mechanism of DKTP during PMS treatment. The loss of learning and memory, the decreased estrous and uterine coefficient, and the presence of histopathological changes suggests a successful establishment of rat PMS model. Following DKTP or nilestriol treatment, the above results were reversed. E2 level in serum, uterine, and ovarian tissues was upregulated upon different concentrations of DKTP treatment, indicating that DKTP promotes the E2 level in a dose-dependent manner. DKTP also increased the expression of ER, CYP17, CYP11A1, CYP19, 17HSD, STS, and SHGB while decreased the GnRHR expression in uterine and ovarian tissues, revealing that these key molecules involved in estrogen synthesis, metabolism, and transport in PMS rats. We confirmed the anti-PMS effect of DKTP through enhancing E2 production. Exploring a novel drug based on improving E2 synthesis, metabolism, and transport may represent a novel strategy for PMS prevention and treatment.
围绝经期综合征（PMS）发病率高，影响中老年女性身心健康。PMS的阻断对改善围绝经期女性健康具有重要意义。目前，对于PMS的防治，中医因其安全性和有效性已成为理想选择。本研究旨在探讨滋阴补肾汤（DKTP）抗PMS的作用及其潜在机制。将30只雌性Wistar大鼠分为5组（每组6只）：对照组、低剂量DKTP组、中剂量DKTP组、高剂量DKTP组和尼尔雌醇组。使用雌二醇（E2）放射免疫分析试剂盒分析大鼠外周血中E2水平，通过苏木精-伊红染色检查子宫形态变化。通过莫里斯水迷宫（MWM）和新物体识别（NOR）任务评估大鼠的学习和记忆能力。评估与E2合成、代谢和转运相关的雌激素受体α（ER）、GnRHR、CYP17、CYP11A1、CYP19、17HSD、STS和SHGB，以探讨DKTP在PMS治疗期间促进E2的机制。学习和记忆丧失、动情和子宫系数降低以及组织病理学变化的存在表明成功建立了大鼠PMS模型。DKTP或尼尔雌醇治疗后，上述结果得到逆转。不同浓度DKTP处理后，血清、子宫和卵巢组织中的E2水平上调，表明DKTP以剂量依赖方式促进E2水平。DKTP还增加了子宫和卵巢组织中ER、CYP17、CYP11A1、CYP19、17HSD、STS和SHGB的表达，同时降低了GnRHR的表达，揭示了这些关键分子参与PMS大鼠雌激素的合成、代谢和转运。我们通过增强E2产生证实了DKTP的抗PMS作用。探索基于改善E2合成、代谢和转运的新型药物可能代表PMS防治的新策略。
