目的 探討坤泰膠囊對注射用環(huán)磷酰胺致卵巢儲備功能低下大鼠的治療作用及機制。方法 將60只12周齡SD雌性大鼠隨機分為對照組、模型組和坤泰膠囊高、中、低劑量（1.2、0.6、0.3 g/kg）組、結(jié)合雌激素片組，ip注射用環(huán)磷酰胺建立卵巢儲備功能低下大鼠模型，各給藥組于造模14 d后分別ig給藥，連續(xù)給藥36 d。觀察大鼠一般狀態(tài)、體質(zhì)量改變，定期行陰道涂片觀察大鼠動情周期的變化；酶聯(lián)免疫吸附法（ELISA）檢測大鼠血清性激素抗穆勒管激素（AMH）、卵泡刺激素（FSH）、黃體生成激素（LH）、雌二醇（E₂）水平變化；光鏡下觀察卵巢形態(tài)與卵泡數(shù)；實時熒光定量PCR（qRT-PCR）檢測大鼠卵巢生長分化因子9（GDF-9）、早期生長反應(yīng)因子1（Egr-1）mRNA表達(dá)水平的變化；免疫組化法檢測大鼠卵巢GDF-9、Egr-1蛋白表達(dá)水平的變化。結(jié)果 與模型組比較，坤泰膠囊組大鼠精神逐漸好轉(zhuǎn)，飲食恢復(fù)正常，毛色有光澤，大便色深；體質(zhì)量漸增，差異顯著（P<0.05）；動情周期紊亂得到明顯改善（P<0.05）；卵巢存在成熟卵泡，卵泡腔內(nèi)卵子生長良好；大鼠血清FSH、LH水平明顯降低，E₂、AMH水平明顯升高，差異有統(tǒng)計學(xué)意義（P<0.05）；GDF-9、Egr-1蛋白及基因表達(dá)明顯增加，差異有統(tǒng)計學(xué)意義（P<0.05），且作用均呈劑量相關(guān)性，高劑量組治療效果與結(jié)合雌激素片無明顯差距。結(jié)論 坤泰膠囊能夠修復(fù)大鼠受損的卵巢組織結(jié)構(gòu)，提高成熟卵泡存在數(shù)量，改善大鼠動情周期及激素水平，機制可能與增加GDF-9、Egr-1表達(dá)相關(guān)。

Objective To explore the therapeutic effects and mechanism of Kuntai Capsules on ovarian reserve dysfunction in rats induced by cyclophosphamide injection. Methods The 60 12-week-old SD female rats were randomly divided into control group, model group, Kuntai Capsules high, middle, and low dose (1.2, 0.6, and 0.3 g/kg) groups, and estrogen group. Cyclophosphamide peritoneal injection was used to establish the model of ovarian reserve dysfunction. Rats in each drug group were ig administrated successively for 36 d after 14 d of modeling. During the experiment, the behavior and the changes of body mass of ratswere observed. Regular vaginal smear was done to observe the changes of estrus cycle in rats. Serum sex hormone levels changes of antimullerian hormone (AMH), and follicle-stimulating hormone (FSH), luteinizing hormone (LH), and Estradiol (E₂) were detected by enzyme-linked immunosorbent assay (ELISA). The ovary morphology and follicular number were observed under light microscope. Real-time fluorescence quantitative PCR (qRT-PCR) was used to detect the changes in mRNA expression levels of growth differentiation factor 9 (GDF-9) and early growth response gene 1 (Egr-1) in rats. The expression levels of GDF-9 and Egr-1 in rats were measured by immunohistochemistry. Results Compared with the model group, the spirit of the rats in the Kuntai Capsules group gradually improved, the diet was restored to normal, the hair color was luster, the color of the stool was deep, the body mass was increasing, the difference was significant (P<0.05); The disorder of the estrous cycle was obviously improved (P<0.05); The ovary had mature follicles and the follicles grew well in the follicle cavity; The level of FSH and LH in the serum of rats decreased significantly, the level of E₂ and AMH increased significantly (P<0.05), and the expression of GDF-9, Egr-1 protein and gene increased significantly (P<0.05), and the effect was in a dose-dependent manner. There were no significant therapeutic effects between Kuntai Capsules high dose group and Conjugated Estrogens Tablets group. Conclusion Kuntai Capsules could repair damaged ovarian tissue of rats structure, increase the number of mature follicles, and improve estrous cycle and hormone level in rats, which may be related to the increased expression of GDF-9 and Egr-1.

河北省中醫(yī)藥管理局中醫(yī)藥類科研計劃課題（2016068）；國家中醫(yī)藥管理局全國名老中醫(yī)藥專家高慧傳承工作室建設(shè)項目（2015048157）；河北省省級重大醫(yī)學(xué)科研項目（zyzd2013018）；河北省政府資助臨床醫(yī)學(xué)優(yōu)秀人才培養(yǎng)項目（2014571024）。