当归芍药散对制动应激复合半乳糖诱导的卵巢储备功能下降模型小鼠的干预作用

Intervention effect of Danggui Shaoyao Powder on diminished ovarian reserve model mice induced by immobilization stress combined with galactose

目的探讨当归芍药散对制动应激复合半乳糖诱导的卵巢储备功能下降(DOR)模型小鼠的干预作用。方法选取60只正常动情周期的昆明小鼠,随机挑选10只小鼠为空白组,其余50只小鼠通过制动应激复合注射半乳糖建立DOR模型。造模结束后将模型小鼠随机分成模型组、中药高剂量组、中药中剂量组、中药低剂量组、西药组,各10只。中药高剂量组、中药中剂量组、中药低剂量组分别给予24.44 g/(kg·d)、12.22 g/(kg·d)、6.11 g/(kg·d)的当归芍药散灌胃,西药组给予0.13 mg/(kg·d)戊酸雌二醇灌胃,空白组、模型组小鼠给予等体积蒸馏水灌胃,连续干预4周。记录干预前后各组小鼠的一般情况。干预结束后,观察各组小鼠卵巢组织的形态学变化,并计算卵巢指数,检测血清卵泡刺激素(FSH)、黄体生成素(LH)、雌激素、抗米勒氏管激素(AMH)、抑制素B水平。结果与空白组相比,模型组小鼠动情周期紊乱、卵巢指数下降、闭锁卵泡增多、生长卵泡减少,血清FSH、LH水平升高,而血清雌激素、抑制素B和AMH水平降低。与模型组相比,各药物干预组小鼠动情周期恢复正常、闭锁卵泡减少、生长卵泡增多,且中药低剂量组小鼠卵巢指数上升、血清雌激素和抑制素B水平升高,中药中剂量组小鼠血清FSH水平降低、血清雌激素水平升高,中药高剂量组小鼠血清FSH水平降低、AMH水平升高,西药组小鼠血清FSH水平降低(均P<0.05)。结论当归芍药散可能通过调节DOR模型小鼠下丘脑-垂体-卵巢轴功能,来减少闭锁卵泡数目、增加生长卵泡数目,以及降低血清FSH水平,升高血清雌激素、AMH、抑制素B水平,从而改善卵巢储备功能。

Objective To explore the intervention effect of Danggui Shaoyao Powder on diminished ovarian reserve(DOR)model mice induced by immobilization stress combined with galactose.Methods A total of 60 Kunming mice in normal estrous cycle were selected,and 10 mice were randomly selected as blank group,the remaining 50 mice received immobilization stress and injection of galactose to establish DOR model.After the end of modeling,model mice were randomly assigned to model group,high-dose Traditional Chinese Medicine group,medium-dose Traditional Chinese Medicine group,low-dose Traditional Chinese Medicine group,or Western Medicine group,with 10 mice in each group.Danggui Shaoyao Powder of 24.44 g/(kg·d),12.22 g/(kg·d),and 6.11 g/(kg·d)was intragastrically administrated to the high-,medium-,and low-dose Traditional Chinese Medicine groups,respectively,and the Western Medicine group received intragastric administration of 0.13 mg/(kg·d)estradiol valerate,as well as mice in the blank and model groups received intragastric administration of distilled water with equivalent volume,for a 4-week continuous intervention.The general conditions of mice before and after intervention were recorded.After the end of intervention,morphological changes of ovarian tissues of mice in various groups were observed,and ovarian index of mice in various groups was calculated,as well as the levels of serum follicle-stimulating hormone(FSH),luteinizing hormone(LH),estrogen,anti-Müllerian hormone(AMH),and inhibin B of mice in various groups were detected.Results Compared with the blank group,mice in the model group presented as disturbed estrous cycle,decreased ovarian index,increased atretic follicles,and decreased growing follicles,as well as elevated levels of serum FSH and LH,while decreased levels of serum estrogen,inhibin B,and AMH.Compared with the model group,mice in the various drug intervention groups presented as normal estrous cycle,decreased atretic follicles,increased growing follicles,and elevated ovarian index and levels of serum estrogen and inhibin B in the low-dose Traditional Chinese Medicine group,as well as decreased level of serum FSH and elevated level of serum estrogen in the medium-dose Traditional Chinese Medicine group;moreover,decreased level of serum FSH and elevated level of serum AMH in the high-dose Traditional Chinese Medicine group,and decreased level of serum FSH in the Western Medicine group(all P<0.05).Conclusion Danggui Shaoyao Powder may through regulating the function of hypothalamus-pituitary gland-ovarian axis of DOR model mice to reduce the number of atretic follicles,and increase the number of growing follicles,as well as to decrease the level of serum FSH,and increase the levels of serum estrogen,AMH,and inhibin B,so as to improve the ovarian reserve function.