卵巢早衰大鼠模型建立及中医月经不调气血亏虚型模型初探

Establishment of a Rat Model of Premature Ovarian Failure and a Preliminary Study on a Model of Qi and Blood Deficiency with Irregular Menstruation in Chinese Medicine

目的建立有效、稳定的卵巢早衰大鼠模型,为后续研究提供实验载体,并进一步探析其中医理论依据。方法将雌性SD大鼠随机分为4组,分别为空白对照组、顺铂高剂量组(4 mg/kg,腹腔注射)、顺铂中剂量组(3 mg/kg,腹腔注射)及顺铂低剂量组(2.5 mg/kg,腹腔注射),空白对照组予以同等体积的生理盐水进行腹腔注射,连续注射7 d后,正常喂养21 d,检测大鼠阴道上皮细胞形态与数量,血清雌二醇、促卵泡生成素水平及大鼠卵巢病理学改变。结果与顺铂高、低剂量组相比,顺铂中剂量组连续腹腔注射7 d后,大鼠毛发杂乱无光泽、唇爪苍白、倦怠懒动,动情周期明显改变,血清雌二醇明显降低,促卵泡生成素明显升高,卵巢中成熟卵泡明显减少,闭锁卵泡增多,且存活率为100%。结论中剂量(3 mg/kg)顺铂连续腹腔注射7 d为卵巢早衰大鼠模型较为理想的造模方法,具有更方便、更省时、更稳定等优势;同时,本实验模型与中医气血亏虚证型高度一致,因此建议将顺铂3 mg/kg连续腹腔注射7 d作为中医证候气血亏虚型POF的基本造模方式。

Objective To establish an effective and stable rat model of premature ovarian failure,to pro-vide an experimental carrier for the follow-up study,and to investigate its theoretical basis in Chinese medicine.Methods Female SD rats were randomly divided into four groups:a blank control group,a high-dose cisplatin group(4 mg/kg,intraperitoneal injection),a medium-dose cisplatin group(3 mg/kg,intraperitoneal injec-tion),and a low-dosecisplatin group(2.5 mg/kg,intraperitoneal injection).The same volume of saline was injected intraperitoneally into the blank control group,and the rats were fed normally for 21 days after the injec-tions for 7 consecutive days.The morphology and the number of epithelial cells,the serum estradiol and follicle stimulating hormone levels,as well as the pathological changes in the ovaries of rats were examined.Results Compared with the high-dose and low-dose cisplatin groups,after continuous intraperitoneal injection of cispla-tin for 7 days,the hair of the rats was dishevelled and lustrous,the lips and PAWS were pale,the estrus cycle was significantly changed,the serum estradiol was significantly reduced,the follicle-stimulating hormone was significantly increased,the mature follicles of the ovaries were significantly reduced,and the atretic follicles were increased,and the survival rate was 100%.Conclusion A moderate dose of cisplatin(3 mg/kg)intraper-itoneally for 7 days is a more convenient,time-saving,and stable method for creating a rat model of premature ovarian failure(POF)compared to other modeling methods.At the same time,this experimental model is highly consistent with the syndrome of deficiency of qi and blood in traditional Chinese medicine,so it is suggested that cisplatin 3 mg/kg intraperitoneally for 7 days be used as the basic modeling method for POF with syndrome of deficiency of qi and blood in traditional Chinese medicine.