戊酸雌二醇片/雌二醇环丙孕酮片对卵巢早衰小鼠激素水平和肠道菌群的调节作用

Regulatory effects of estradiol valerate tablets/estradiol-cyproterone tablets on hormone levels and intestinal flora in mice with premature ovarian failure

目的探究戊酸雌二醇片/雌二醇环丙孕酮片对环磷酰胺诱导的卵巢早衰(POF)小鼠激素水平和肠道菌群的调节作用。方法将24只C57BL/6小鼠随机分为对照组、模型组和治疗组,每组8只。对照组不作任何处理。模型组和治疗组小鼠通过连续15 d腹腔注射环磷酰胺(50 mg·kg-1·d-1)建立POF模型。造模结束7 d后,治疗组小鼠戊酸雌二醇片(0.13 mg·kg-1·d-1)和雌二醇环丙孕酮片(0.65 mg·kg-1·d-1)灌胃。观察小鼠一般情况并称体质量;ELISA法检测小鼠血清中卵泡刺激素(FSH)和雌二醇(E2)水平;HE染色观察卵巢形态,并统计各级卵泡数量;16S rRNA测序分析小鼠肠道菌群的多样性。结果与对照组比较,模型组小鼠体质量降低,FSH升高,E2降低,发育、成熟卵泡减少,闭锁卵泡增加,厚壁菌门与拟杆菌门的相对丰度含量比值(F/B)升高,Muribaculaceae丰度降低,Lachnospiraceae、Alistipes丰度升高,差异均有统计学意义(均P<0.05);与模型组比较,治疗组小鼠体质量增加,FSH降低,E2升高,发育卵泡增加,闭锁卵泡减少,F/B降低,Muribaculaceae丰度升高,Lachnospiraceae、Alistipes丰度降低,差异均有统计学意义(均P<0.05)。结论戊酸雌二醇片/雌二醇环丙孕酮片能改善环磷酰胺诱导的小鼠POF,调节激素水平,提高卵巢储备功能,调节肠道菌群失调,其改善机制可能与减轻POF小鼠肠道炎症反应、增加有益菌的定植有关。

Objective To explore the regulatory effects of estradiol valerate tablets/estradiol-cyproterone tablets on hormone levels and intestinal flora in mice with cyclophosphamide-induced premature ovarian failure(POF).Methods Twenty-four C57BL/6 mice were divided into control,model,and treatment groups,with eight mice in each group.Mice in the control group were not treated,and those in the model and treatment groups received intraperitoneal injections of 50 mg·kg-1·d-1 cyclophosphamide for 15 days to establish the POF model.Seven days after establishment of the model,the mice in the treatment group received intragastric administration of 0.13 mg·kg-1·d-1 estradiol valerate tablets and 0.65 mg·kg-1·d-1 estradiol-cyproterone tablets.The general condition of the mice was observed,and body weight was recorded.ELISA was performed to detect serum follicle-stimulating hormone(FSH)and estradiol(E2)levels.HE staining was performed to count the number of follicles.16S rRNA sequencing was performed to analyze the diversity of intestinal flora.Results Compared with the control group,body weight,E2,developing and mature follicles,and Muribaculaceae significantly decreased,and FSH,atretic follicles,F/B,and Lachnospiraceae and Alistipes significantly increased in the model group(P<0.05).Compared with the model group,body weight,E2,developmental follicles,and Muribaculaceae significantly increased,and FSH,atretic follicles,F/B,and Lachnospiraceae and Alistipes significantly decreased in the treatment group(P<0.05).Conclusion Estradiol valerate tablets/estradiolcyproterone tablets can improve cyclophosphamide-induced POF in mice,regulate hormone levels,improve ovarian reserve function,and regulate imbalances in intestinal flora.Regulatory mechanisms may be related to reducing intestinal inflammation and increasing colonization of beneficial bacteria in POF mice.