Page 46 - 《中国药房》2021年第1期

Study on Improvement Effects and Mechanism of Guizhi Fuling Pills on Phlegm-dampness Type PCOS
Model Rats
1，2
3
3
1
YU Jingwei ，ZHONG Xiaoying ，ZENG Lei ，ZHENG Yongxia（1. Dept. of TCM Gynecology，He Xian
Memorial Hospital of Panyu District of Guangzhou，Guangzhou 511400，China；2. Science and Technology
Industrial Park of Guangzhou University of TCM，Guangzhou 510445；3. First College of Clinical Medicine，
Guangzhou University of TCM，Guangzhou 510405，China）
ABSTRACT OBJECTIVE：To study the improvement effect and mechanism of Guizhi fuling pill （GZFLP） on rats with
phlegm-dampness type polycystic ovary syndrome（PCOS）.METHODS：Totally fifty female SD rats with regular estrous cycle were
randomly divided into blank control group （n＝10） and model group （n＝40）. The model group received letrozole
intragastrically [1 mg/（kg·d），for 21 d ] to induce phlegm-damp PCOS rat model. Forty model rats were randomly divided into
model group，metformin group [positive control，0.135 g/（kg·d）] and GZFLP low-dose，high-dose groups [4.49，17.96 g/（kg·
d）]，with 10 rats in each group. Each medicine group was given intragastric administration，once a day，for 30 consecutive days.
Blank control and model group were given intragastric administration of equal volume normal saline.After last medication，oral
glucose tolerance test（OGTT）was used to detect the level of blood glucose in rats at 0，30，60 and 120 min. ELISA assay was
used to detect the levels of follicle-stimulating hormone（FSH），luteinizing hormone（LH），estradiol（E2 ）and testosterone（T）；
body weight，the weight of uterus，bilateral ovaries and paragonadal fat were weighed. HE staining was used to observe
morphological changes of ovarian tissue sections. RT-PCR method and Western blotting assay were used to detect mRNA and
protein expression of CYP19a1 in ovary and Glut4 in uterine. RESULTS：Compared with blank control group，the levels of blood
glucose 30，60，120 min after intragastric administration of glucose solution as well as serum levels of LH，E2 and T were
increased significantly in model group（P＜0.05）；the body weight，the weight of uterus，bilateral ovaries and paragonadal fat
were increased significantly（P＜0.05）；the volume of thecal cells increased significantly and showed spherical shape；the mRNA
and protein expression of CYP19a1 in ovarian tissue and Glut4 in uterine tissue were decreased significantly（P＜0.05 or P＜0.01）.
Compared with model group，above indexes of administration groups were improved significantly （P＜0.05 or P＜0.01）；the
thickness of theca cell layer and the volume of theca cells in GZFLP low-dose and high-dose groups were also improved.
CONCLUSIONS：GZFLP can up-regulate the expression of CYP19a1 in ovary and Glut4 in uterus，so as to improve the abnormal
glucose metabolism in phlegm-dampness type PCOS model rats，reduce insulin resistance，lower serum estrogen levels，and reduce
the degree of polycystic changes in ovary，thereby playing a role in the treatment of PCOS.
KEYWORDS Guizhi fuling pills；Phlegm-dampness type polycystic ovarian syndrome；Insulin resistance；Aromatase；Glucose
transporter 4

多 囊 卵 巢 综 合 征（Polycystic ovary syndrome， 雄激素水平，从而有效改善卵巢功能、提高妊娠成功率，
PCOS）是一种常见的内分泌紊乱综合征，好发于青春期 对 PCOS 预后有积极作用 [16-17] 。但是，目前并未有将桂
及育龄期妇女，以卵巢功能障碍和代谢异常为特征，多 枝茯苓丸与中医痰湿型 PCOS 证候联系在一起的研究。
伴有持续性排卵障碍、高雄激素血症、高胰岛素血症、肥 鉴于此，本课题组以动物实验为基础，从血清甾体激素
胖和卵巢多囊样改变等表现 [1-2] 。已有研究证实，芳香化 水平、卵巢形态学变化、卵巢组织中 CYP19a1 和子宫组
酶（CYP19a1）、葡萄糖转运蛋白4（Glut4）、亚甲基四氢叶 织中 Glut4 的 mRNA 及蛋白表达等角度，探讨桂枝茯苓
酸还原酶（MTHFR）等基因的表达变化与 PCOS 的发病 丸对痰湿型 PCOS 大鼠的改善作用及可能机制，为桂枝
有一定的相关性 [3-5] 。PCOS 的总体发病率为 8％～ 茯苓丸的临床推广应用提供实验依据。
[7]
[6]
13％ ，是导致无排卵性不孕最常见的原因 ，并能显著 1 材料
增加2型糖尿病、心脑血管疾病、卵巢癌等远期并发症的 1.1 仪器
风险 [8-9] 。现代中医研究认为，痰湿是PCOS的主要病因 XMark型酶标仪（美国Bio-Rad公司）；PIDRed 96型
之一 [10-11] ，与非痰湿证患者相比，痰湿证患者肥胖的发生 聚合酶链式反应（PCR）扩增仪（德国 Biometra 公司）；
率更高，且胰岛素抵抗、糖脂代谢异常的程度较重，呈正 RM2245 型冰冻切片机（北京世贸远东科学仪器有限公
相关关系 [12-13] 。因此，PCOS临床治疗多以改善胰岛素抵 司）；EG1150 型包埋机、SM2000R 型石蜡滑动式切片机
抗、调节内分泌代谢水平等为原则 [14-15] 。 （德国Leica公司）；BX-2型生物显微镜（日本Olympus公
桂枝茯苓丸是源自《金匮要略》的经典名方，由桂 司）；Quintix 型电子天平（德国 Sartorius 公司）；CF10 型
枝、茯苓、芍药、桃仁、牡丹皮组成，广泛用于妇产科等疾 全自动分析仪（武汉明德生物有限公司）；ZF-208型凝胶
病的治疗。临床报道显示，桂枝茯苓丸有活血化瘀、消 成像系统（上海恒勤仪器设备有限公司）。
癓散积之功效，能够增加胰岛素敏感性、减轻炎症反应 1.2 药品与试剂
及氧化应激反应、改善胰岛素抵抗、降低体内胰岛素与 桂枝茯苓丸（明致集团万荣药业有限公司，批号：

·40 · China Pharmacy 2021 Vol. 32 No. 1 中国药房 2021年第32卷第1期