归肾丸对卵巢储备功能低下小鼠学习记忆能力和骨密度的影响

Effects of Gui-shen-wan on Learning and Memory Capacity and Bone Density in Mice with Diminished Ovarian Reserve

目的探索归肾丸对卵巢储备功能低下小鼠学习记忆能力和骨密度的影响。方法将40只C57BL/6J雌性小鼠随机分为正常组、模型组、归肾丸组和脱氢表雄酮(DHEA)组。连续序贯腹腔注射孕马血清、人绒毛膜促性腺激素、前列腺素F2α诱导连续超促排卵,再结合臭氧吸入构建卵巢功能衰退模型。其后归肾丸组与DHEA组给予相应药物灌胃(0.3mL/d),而正常组与模型组生理盐水灌胃(0.3mL/d),共21d。观察各组小鼠体重、动情周期、血清卵泡刺激素(FSH)水平、黄体生成素(LH)水平、卵巢组织形态学变化,以及观察小鼠记忆力与骨质情况的变化。结果与模型组相比,归肾丸组及DHEA组血清FSH、LH水平均明显降低,始基卵泡与初级卵泡数均明显增加(P<0.05或P<0.01);归肾丸组与DHEA组学习记忆力及骨密度情况均较模型组有明显改善(P<0.05或P<0.01)。结论归肾丸对卵巢储备功能低下模型小鼠具有明显的治疗作用,可改善小鼠学习记忆力以及骨质情况,其机制可能与改善动情周期及血清FSH、LH水平有关。

Objective To investigate the effects of Gui-shen-wan on learning and memory capacity and bone density in mice with diminished ovarian reserve （DOR）. Methods Forty female C57BL/6J mice were randomly divided into 4 groups, i.e. normal group, model group, Gui shen-wan group and dehydroepiandrosterone（DHEA） group. DOR models were established by sequentially administrating pregnant mare serum gonadotropin （PMSG）, human chorionic gonadotropin （HCG）, and prostaglandin F2a （PGF2a） and then exposing to ozone. Mice in Oui-shen-wan group and DHEA group were intragastrically administered with corresponding drugs （0.3 mL/d）, while those in normal group and model group received the same amount of saline for 21 days. The changes of body weight, oestrous cycle, serum levels of follicle stimulating hormone （FSH） and luteinizing hormone （LH）, and ovarian histomorphology were observed. The learning and memory capacity and the bone density were detected by Morris water maze testing and Micro-CT, respectively. Results The serum levels of FSH and I.H were significantly decreased and the number of the primordial follicle and primary follicle significantly increased in Gui-shen-wan and DHEA groups when compared with those in model group （P〈0.05）. The learning and memory capacity and the bone density were significantly improved in Gui shen-wan and DHEA groups relative to model group （P〈0.05）. Conclusion Oui shen-wan is effective in treatment of mice with DOR. It can improve the learning and memory capacity and bone density in mice with DOR, which involves the effects on the oestrous cycle and the serum levels of FSH and LH.