基于PI3K/Akt/mTOR研究毓麟养巢针药治疗大鼠早发性卵巢功能不全及机制  

Function and mechanism investigation of acupuncture and decoction of Yulin Yangchao on premature ovarian insufficiency rats via PI3K/Akt/mTOR pathway

作　　者：黄艳辉[1] 吴绘春 朱慧香 李淑毅 田永强 HUANG Yanhui;WU Huichun;ZHU Huixiang;LI Shuyi;TIAN Yongqiang(Department of Gynecology,Wuhan Hospital of Traditional Chinese Medicine,Hubei Wuhan 430061,China;Department of Pharmacy,Wuhan Hospital of Traditional Chinese Medicine,Hubei Wuhan 430061,China)

机构地区：[1]武汉市中医医院妇科,湖北武汉430061 [2]武汉市中医医院药学部,湖北武汉430061

出　　处：《中国医院药学杂志》2024年第14期1620-1626,共7页Chinese Journal of Hospital Pharmacy

基　　金：国家中医药管理局第五批全国中医临床优秀人才研修项目(编号:国中医药人教函[2022]1号);武汉市科技计划项目(编号:2020020601012300);武汉市卫生健康委员会医学科研项目(编号:MZ20M02、WZ21A03)。

摘　　要：目的:基于PI3K/Akt/mTOR,探讨毓麟养巢针、药对POI大鼠的卵巢功能恢复及机制。方法:将雌性Wistar大鼠按随机数字表法随机分为正常组、模型组、中药组、针刺组、针药组、西药组。采用环磷酰胺腹腔注射造模成功后,中药组、针刺组和针药组分别给以相应的中药煎剂10 mL(19.85 g生药)·kg^(-1)·d^(-1)灌胃、针刺及中药灌胃联合针刺,正常组、模型组予生理盐水10 mL·kg^(-1)·d^(-1)灌胃,西药组予芬吗通配液后10 mL·kg^(-1)·d^(-1)灌胃,连续4周。取各组大鼠卵巢、子宫进行HE染色,ELISA法检测血清性激素水平,蛋白免疫印迹法检测卵巢p-PI3k、p-Akt、p-mTOR及Bax、Bcl-2水平。结果:与模型组比较,各处理组大鼠体质量、脏器湿质量和脏器指数改善(P<0.05),子宫、卵巢形态明显恢复,各级生长发育的卵泡和黄体数量增加,AMH、E2、INH-B、p-PI3k、p-Akt及p-mTOR、Bcl-2水平升高(P<0.05),FSH、LH、Bax明显降低(P<0.05);同时,各中医药组具有与西药组相当或更强的治疗作用,且针药组各指标回调优于针刺组、中药组、西药组(P<0.05)。结论:毓麟养巢针、药,通过回调PI3K/Akt/mTOR介导的Bax/Bcl-2表达,改善卵巢功能;二者结合比针或药单独使用,可显著改善POI大鼠卵巢功能。OBJECTIVE To explore the pharmacodynamics and potential mechanisms of Yulin Yangchao for premature ovarian insufficiency(POI)on the basis of PI3K/Akt/mTOR pathway.METHODS Female Wistar rats were randomized into 6groups of normal,model,traditional Chinese medicine(TCM),acupuncture(A),traditional Chinese medicine plus acupuncture(TCMA)and medicine(M,Fenmatong)according to randomized digital table.POI model was established by an intraperitoneal injection of cyclophosphamide.Then intra-gastric TCM dosing(10 mL·kg^(-1)·d^(-1))and acupuncture were offered based on groups,respectively.And saline was dosed for normal and model groups.Fenmatong was dosed for M group.Four weeks later,sera samples and ovary and uterine tissues were collected.Hematoxylin-eosin(HE),enzyme-linked immunosorbent assay(ELISA)and Western blot were utilized for detecting the morphology,hormone content and expressions of p-PI3k,p-Akt,pmTOR,Bcl-2-associated X protein(Bax)and Bcl-2.RESULTS Results of body weight,uterine morphology,ovarian morphology,organ wet weight and organ index improved(P<0.05).Up-regulations of follicle count,corpus luteum count,antiMullerian hormone(AMH),estradiol(E2),INHB(INH-B),p-PI3k,p-Akt,p-mTOR and Bcl-2 were validated(P<0.05)while down-regulations of follicle-stimulating hormone(FSH),luteinizing hormone(LH)and Bax confirmed(P<0.05).The overall results of treatment groups indicated that a combination of acupuncture and decoction was superior to Fenmatong(positive control)in curing potential on POI(P<0.05).CONCLUSION Decoction and acupuncture of Yulin Yangchao may reverse an imbalance of Bax/Bcl-2 via mediating PI3K/Akt/mTOR pathway and improve ovarian function in POI rats.A combination of Yulin Yangchao Decoction and acupuncture offer optimal effects of mitigating the dysfunction and restoring ovarian function for POI.

关 键 词：早发性卵巢功能不全 毓麟养巢针 毓麟养巢方 PI3K/AKT/MTOR BAX/BCL-2 

分 类 号：R96[医药卫生—药理学] R245[医药卫生—药学]