Page 66 - 《中国药房》2022年19期

固本安神方对绝经综合征模型大鼠的改善作用机制研究 Δ

郭珊珊 ，周晓辉，王淑梅，宗传杰，刁 丽（沧州市人民医院药物临床试验机构，河北 沧州 061000）
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中图分类号 R965 文献标志码 A 文章编号 1001-0408（2022）19-2364-05
DOI 10.6039/j.issn.1001-0408.2022.19.12

摘 要 目的 研究固本安神方对绝经综合征模型大鼠的改善作用及机制。方法 随机取70只大鼠切除双侧卵巢以复制绝经综
合征模型，另取10只未造模大鼠作为假手术组。将造模成功的60只大鼠分为模型组、更年安片组（中药阳性对照组，0.56 g/kg）、
戊酸雌二醇片（化学药阳性对照组，0.1 mg/kg）和固本安神方高、中、低剂量组（18.0、9.0、4.5 g/kg），每组10只。模型组和假手术组
大鼠灌胃生理盐水，各给药组大鼠灌胃相应药物，每天1次，连续4周。末次给药后，检测大鼠血浆中促黄体生成素（LH）、促卵泡
生长激素（FSH）、雌二醇（E2 ）含量，检测大鼠子宫、肾上腺、脾、胸腺脏器指数，观察大鼠子宫组织病理形态学变化，检测大鼠下丘
脑组织中亲吻素 1（Kiss-1）、三磷酸肌醇受体 1（IP3R1）、促性腺激素释放激素（GnRH）mRNA 及 Kiss-1、细胞外调节蛋白激酶 1/2
（ERK1/2）、磷酸化 ERK1/2（p-ERK1/2）蛋白的表达水平。结果 与假手术组比较，模型组大鼠血浆中 LH、FSH 含量均显著升高
（P＜0.05 或 P＜0.01），E2含量、各脏器指数以及下丘脑组织中 Kiss-1、IP3R1、GnRH mRNA 和 Kiss-1、p-ERK1/2 蛋白的表达水平均
显著降低（P＜0.05或P＜0.01）；子宫腺体减少、固有层细胞密集。与模型组比较，固本安神方各剂量组大鼠上述指标水平（低剂量
组E2含量除外）均显著逆转（P＜0.05或P＜0.01）；子宫腺体增多，单层柱状上皮细胞排列较为整齐（低剂量组除外）。结论 固本安
神方可通过升高大鼠下丘脑组织中Kiss-1、IP3R、GnRH mRNA和Kiss-1、p-ERK1/2蛋白的表达水平，激活GnRH分泌信号通路，从
而改善绝经综合征。
关键词 固本安神方；绝经综合征；促性腺激素释放激素；机制

Study on the improvement effects of Gubenanshen decoction on menopausal syndrome model rats
GUO Shanshan，ZHOU Xiaohui，WANG Shumei，ZONG Chuanjie，DIAO Li（Drug Clinical Trial Institution，
Cangzhou Municipal People’s Hospital，Hebei Cangzhou 061000，China）

ABSTRACT OBJECTIVE To study the improvement effect and mechanism of Gubenanshen decoction on menopausal syndrome
model rats. METHODS Totally 70 rats were anesthetized and placed on the operating table for bilateral ovariectomy to induce
menopausal syndrome model. Other 10 rats without modeling were taken as sham operation group. Sixty model rats were divided
into model group，Gengniananpian group（TCM positive control group，0.56 g/kg），Estradiol valerate tablet group（chemical drug
positive control group，0.1 mg/kg），Gubenanshen decoction high-dose，medium-dose and low-dose groups（18.0，9.0，4.5 g/kg），
with 10 rats in each group. Model group and sham operation group were given normal saline intragastrically；administration groups
were given relevant medicine intragastrically，once a day，for consecutive 4 weeks. After last administration，the plasma contents
of luteinizing hormone （LH），follicle stimulating growth hormone （FSH） and estradiol （E2 ） were determined. The indexes of
uterus，adrenal gland，spleen and thymus were measured；pathological changes of rat uterus were observed；mRNA expressions of
kisspenptin 1 （Kiss-1），inositol triphosphate receptor 1 （IP3R1） and gonadotropin-releasing hormone （GnRH） in hypothalamic
tissues were detected，and the protein expressions of Kiss-1，ERK1/2 and p-ERK1/2 were also detected. RESULTS Compared with
sham operation group，the contents of LH and FSH in the plasma of rats were significantly increased in model group（P＜0.05 or
P＜0.01）. The contents of E2，organ index，mRNA expressions of Kiss-1，IP3R1 and GnRH and protein expressions of Kiss-1 and
p-ERK1/2 were decreased significantly in hypothalamic tissues（P＜0.05 or P＜0.01）. The glands of the uterus were reduced and
the cells in the lamina propria were dense. Compared with model group，above indexes of Gubenanshen decoction groups（except
for the content of E2 in the low-dose group） were reversed significantly （P＜0.05 or P＜0.01）. The number of uterine glands
increased， and single columnar epithelial cells were arranged orderly （except for the low-dose group）. CONCLUSIONS
Gubenanshen decoction can increase mRNA expressions of Kiss-1，IP3R and GnRH and protein expressions of Kiss-1 and p-ERK1/2
in hypothalamic tissues of rats，and activate GnRH secretion
Δ 基金项目 河北省中医药管理局中医药指令性计划课题（No.
signaling pathways so as to improve the menopausal syndrome.
2021288）
＊第一作者 主管中药师。研究方向：临床药理与药学研究。E- KEYWORDS Gubenanshen decoction；menopausal syndrome；
mail：guosss274401519@126.com GnRH；mechanism

·2364· China Pharmacy 2022 Vol. 33 No. 19 中国药房 2022年第33卷第19期