摘要
目的探讨养精种玉汤对顺铂所致卵巢早衰大鼠的作用及其对Akt、mTOR、GnRHR表达的影响。方法大鼠随机分为空白组(7只)和造模组(35只),空白组不予处理,造模组腹腔注射4.0 mg/kg顺铂水溶液,每周1次,共2次。将造模成功的大鼠随机分为模型组、阳性对照组(0.01 mg/mL戊酸雌二醇片水溶液)和养精种玉汤低、中、高剂量组(0.34、0.68、1.35 g/mL),每组7只,各给药组给予相应药物,连续给药21 d。观察大鼠动情周期变化,计算卵巢指数,ELISA法检测血清E_(2)、FSH、AMH及GnRH水平,HE染色观察大鼠卵巢组织病理形态,免疫组化法检测大鼠卵巢组织Akt、mTOR、GnRHR蛋白表达,RT-qPCR法检测大鼠卵巢组织Akt、mTOR、GnRHR mRNA表达。结果与空白组比较,模型组大鼠血清E_(2)、AMH水平降低(P<0.01),FSH、GnRH水平升高(P<0.01),卵巢组织Akt、mTOR、GnRHR蛋白和mRNA表达降低(P<0.01)。与模型组比较,各给药组大鼠卵巢内成熟卵泡数量增多,闭锁卵泡数量减少,卵巢指数均增加(P<0.05,P<0.01);养精种玉汤高剂量组大鼠血清E_(2)、AMH水平升高(P<0.01),FSH、GnRH水平降低(P<0.01),卵巢组织Akt、mTOR、GnRHR蛋白和mRNA表达升高(P<0.05,P<0.01)。结论养精种玉汤能改善卵巢早衰大鼠病理形态,提高卵巢储备功能,其机制可能与调控下丘脑-垂体-卵巢轴功能状态,从而调节大鼠激素水平,改善内分泌紊乱,减少颗粒细胞凋亡,促进卵泡发育有关。
AIM To explore the effects of Yangjing Zhongyu Decoction on rat model of premature ovarian failure induced by cisplatin and its influence on the expressions of Akt,mTOR and GnRHR.METHODS The rats were randomly divided into the blank group(7 rats)for no more treatment;and the model group(35 rats)for intraperitoneal injection of 4.0 mg/kg cisplatin solution once a week,twice in total.Subsequently,the successful rat models were randomly divided into the model group,the positive control group(0.01 mg/mL aqueous solution of estradiol valerate tablets)and low,medium and high dose groups of Yangjing Zhongyu Decoction(0.34,0.68,1.35 g/mL),with 7 rats in each group,for 21 days corresponding drug administration.The rats had their changes of estrous cycle observed;their ovarian index level calculated;their serum E_(2),FSH,AMH and GnRH levels detected by ELISA;their ovarian pathological morphology observed by HE staining;their protein expressions of Akt,mTOR and GnRHR detected by immunohistochemistry;and their ovarian mRNA expressions of Akt,mTOR and GnRHR detected by RT-qPCR.RESULTS Compared with the blank group,the model group displayed decreased serum E_(2)and AMH levels(P<0.01);increased FSH and GnRH levels(P<0.01),and reduced relative protein and mRNA expressions of Akt,mTOR and GnRHR in ovarian tissue(P<0.01).Compared with the model group,each intervened group demonstrated increased number of mature follicles,decreased number of atresia follicles,and increased ovarian index level(P<0.05,P<0.01).The high-dose Yangjing Zhongyu Decoction group shared increased serum E_(2)and AMH levels(P<0.01),decreased levels of FSH and GnRH(P<0.01),and increased ovarian relative protein and mRNA expressions of Akt,mTOR and GnRHR(P<0.05,P<0.01).CONCLUSION Upon the rat model of premature ovarian failure,Yangjing Zhongyu Decoction can improve the pathological morphology and ovarian reserve,and its mechanism may be related to its positive impact on hypothalamic-pituitary-ovarian axis controlling the hormone level,the endocrine disorder,the granulosa cell apoptosis,and follicle development.
作者
肖贾丽珏
李涵
周锦宏
刘慧萍
XIAO Jia-li-jue;LI Han;ZHOU Jin-hong;LIU Hui-ping(Hunan University of Chinese Medicine,Changsha 410208,China)
出处
《中成药》
CAS
CSCD
北大核心
2023年第5期1476-1481,共6页
Chinese Traditional Patent Medicine
基金
湖南省自然科学基金面上项目(2022JJ30035)
湖南省中医药科研计划项目重点项目(2021025)
湖南省教育厅科学研究重点项目(21A0233)
湖南中医药大学校级科研基金重点项目(2020XJJJ003)
国家级大学生创新创业计划训练项目(202110541042)
湖南省大学生创新创业计划训练项目(202002010614)
湖南中医药大学研究生创新基金(2021CX66)
湖南中医药大学中西医结合一流学科开放基金项目(2020ZXYJH66,2020ZXYJH71)。
