基于雌激素信号通路传导加味八珍益母胶囊治疗卵巢早衰的作用机制  

Mechanism of Jiawei Bazhen Yimu Capsule in Treatment of Premature Ovarian Failure Based on Estrogen Signaling Pathway

作　　者：韩丽颖 王帅[1,2] 包永睿 李天娇[1,2] 张凌巍 孟宪生[1,2] HAN Liying;WANG Shuai;BAO Yongrui;LI Tianjiao;ZHANG Lingwei;MENG Xiansheng(College of Traditional Chinese Medicine(TCM),Liaoning University of TCM,Dalian 116600,China;Liaoning Professional Innovation Technology Center for Multidimensional Analysis of TCM,Liaoning Modern TCM Research Engineering Laboratory,Dalian11660o,China;Dandong Pharmaceutical Group Co.Ltd.,Dandong118303,China)

机构地区：[1]辽宁中医药大学药学院,辽宁大连116600 [2]辽宁省中药多维分析专业创新技术中心辽宁省现代中药研究工程实验室,辽宁大连116600 [3]丹东药业集团有限公司,辽宁丹东118303

出　　处：《中国实验方剂学杂志》2022年第20期201-208,共8页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：辽宁省揭榜挂帅项目(2021JH1/10400058)。

摘　　要：目的:探讨加味八珍益母胶囊对卵巢早衰雌性大鼠血清性激素、性器官及雌激素信号通路传导的影响。方法:采用网络药理学分析,筛选加味八珍益母胶囊治疗卵巢早衰的关键靶点蛋白。选取雌性健康SD大鼠,采用卵巢摘除术建立大鼠卵巢早衰模型,将50只卵巢摘除的大鼠随机分为模型组,戊酸雌二醇组、加味八珍益母胶囊低、中、高剂量组,另取10只健康雌性大鼠设为假手术组,假手术组和模型组大鼠灌胃蒸馏水、其他给药组大鼠灌胃相应剂量药物。21 d后,测定雌性大鼠血清激素水平,包括雌二醇(E2)、孕激素(P)、卵泡刺激素(FSH)及黄体生成素(LH);免疫荧光染色(IF)检测关键靶点蛋白雌激素受体1(ESR1)、雌激素代谢P4503A4酶(CYP3A4)和P45019A1酶(CYP19A1),在雌性大鼠子宫组织中的蛋白表达水平。结果:与模型组比较,加味八珍益母胶囊低、中、高剂量组明显升高雌性大鼠血清E2、P水平;均可改善雌性大鼠子宫内膜状态;升高雌性大鼠子宫组织中雌激素受体1(ESR1)、激素代谢酶CYP3A4及CYP19A1的阳性表达(P<0.05)。结论:加味八珍益母胶囊治疗卵巢早衰可能与其类激素样作用和激活雌激素信号通路有关。Objective:To investigate the effect of Jiawei Bazhen Yimu capsule on serum sex hormones,sexual organs and estrogen signaling pathway in female rats with premature ovarian failure.Method:The key target proteins of Jiawei Bazhen Yimu capsule in the treatment of premature ovarian failure were screened out by network pharmacology analysis.Female healthy SD rats were selected,and the rat model of premature ovarian failure was established by ovariectomy.Fifty ovariectomized rats were randomly divided into a model group,an estradiol(E2)valerate group,and Jiawei Bazhen Yimu capsule low,medium,and high-dose groups.Another 10 healthy female rats were set as a sham operation group.The sham operation group and the model group were given distilled water by gavage,and other administration groups were given corresponding doses of drugs by gavage.After 21 d,the serum hormone levels of female rats were measured,including E2,progesterone(P),follicle stimulating hormone(FSH),and luteinizing hormone(LH).Immunofluorescence staining(IF)was used to detect the protein expression levels of estrogen receptor 1(ESR1),estrogen metabolism P4503A4 enzyme(CYP3A4),and P45019A1 enzyme(CYP19A1)in the uterine tissues of female rats.Result:As compared with the model group,the serum E2and P levels of female rats in the Jiawei Bazhen Yimu capsule low,medium,and high-dose groups were significantly increased.Jiawei Bazhen Yimu capsule improved the endometrial status of female rats and increased positive expression of ESR1,CYP3A4,and CYP19A1 in the uterine tissues of female rats(P<0.05).Conclusion:The mechanism of Jiawei Bazhenyimu capsule in the treatment of premature ovarian failure may be related to its hormone-like effect and activation of the estrogen signaling pathway.

关 键 词：加味八珍益母胶囊 卵巢早衰 卵巢摘除术 雌激素信号通路 

分 类 号：R285[医药卫生—中药学] R289[医药卫生—中医学] R22R2-031R33