目的：通过卵泡颗粒细胞的凋亡途径探讨二仙汤对化疗性损伤卵巢早衰的影响。方法：将SD大鼠随机分为正常组、模型组、阳性组和二仙汤组，腹腔注射顺铂建立化疗性损伤大鼠卵巢早衰动物模型。造模后连续4周各组灌胃给予相应药物治疗。观察大鼠一般情况；测定血清中E2、FSH、LH和Pro含量；观察卵巢组织形态；TUNEL法分析卵泡颗粒细胞的凋亡；免疫组化检测BAX、Bcl-2和VEGF蛋白的表达情况。结果：模型组体质量下降，动情周期紊乱，治疗后体质量增加，动情周期恢复。与正常组比较，模型组E2、LH下降，FSH水平升高，Pro含量各组比较无显著差异。TUNEL检测模型组较正常组阳性表达增多，二仙汤组较模型组阳性表达减少。模型组较正常组BAX表达明显升高，Bcl-2下降，二仙汤治疗后与模型组比较BAX表达量下降，Bcl-2表达升高；VEGF蛋白在模型组中表达明显低于正常组，二仙汤组较模型组表达增多，阳性组表达略有恢复。结论：顺铂可致卵泡颗粒细胞凋亡，造成卵巢功能过早衰退；二仙汤通过调节血清中各激素含量，改变凋亡细胞相关蛋白的表达量来降低顺铂对卵巢的损害，促进卵泡发育，改善并增强卵巢功能。

This study was aimed to investigate effects of Er-Xian (EX) decoction in follicular granulosa cell apoptosis in chemotherapy-induced premature ovarian failure (POF) of rats. SD rats were randomly divided into the normal group, model group, positive group and EX decoction group. Intraperitoneal injection of cisplatin was used in the establishment of chemotherapy-induced POF rat model. Intragastric administration of corresponding medication was give to each group for four weeks. The general conditions of rats were observed. The serum contents of E2, FSH, LH and Pro were determined. The ovarian tissue morphology was observed. Granulosa cell apoptosis was analyzed by TUNEL. The expressions of BAX, Bcl-2 and VEGF protein were detected by immunohistochemistry. The results showed that in the model group, the body weight decreased with disordered estrous cycle. After treatment, the weight gained, and the estrous cycle recovered. Compared with the normal group, in the model group, E2 decreased, FSH and LH levels increased. There was no significant difference in the content of progesterone among different groups. Detection of TUNEL showed that the positive expression in the model group was increased compared with the normal group (P < 0.05). The positive expression of EX decoction group was reduced compared to the positive group (P<0.05). Compared with the normal group, the expression of BAX was obviously increased and Bcl-2 was decreased in the model group. After EX decoction treatment, the expression of BAX was decreased and the Bcl-2 was increased compared to the model group. The expression of VEGF protein in the model group was obviously less than that in the normal group. It was concluded that cisplatin can induce follicular granulosa cell apoptosis, and cause premature ovarian function recession. EX decoction can adjust the content of different hormones in serum, alter expression of apoptosis related protein to reduce the damage of cisplatin on ovarian follicular development, in order to promote follicular development, improve and enhance the ovarian function.

国家自然科学基金委面上项目（539/02405）：基于PI3K/AKT信号通路探讨二仙汤治疗化疗损伤性卵巢早衰作用机理，负责人：牛建昭；教育部大学生创新性实验计划项目（201310026056）：二仙汤改善大鼠卵巢早衰机制的初步探究，负责人：冒湘琳；北京中医药大学自主选题项目（2013-JYBZZ-JS-006）：通过细胞凋亡途径探讨二仙汤治疗大鼠卵巢早衰实验研究，负责人：张丽娟。