目的 探讨槲皮素通过调控 Janus激酶 2/信号转导和转录激活因子 3（JAK2/STAT3）信号通路对早发性卵 巢功能不全大鼠卵巢功能损伤的改善作用。方法 构建早发性卵巢功能不全大鼠模型并将其随机分为模型组， 槲皮素低（25 mg·kg-1）、中（50 mg·kg-1）、高（100 mg·kg-1）剂量组及槲皮素高剂量+JAK2 通路激活剂 CA1 （100 mg·kg-1槲皮素+4 mg·kg-1 CA1）组，每组 10只大鼠。另取 10只健康大鼠作为对照组。检测所有大鼠的卵 巢系数，血清中促卵泡激素（FSH）、抗缪勒管激素（AMH）、雌二醇（E2）和丙二醛（MDA）、超氧化物歧化酶 （SOD）和过氧化氢酶（CAT）水平，HE染色观察卵巢组织病理变化和各级卵泡（初级、窦前、窦状、成熟、闭锁 卵泡）数量，TUNEL 染色观察卵巢颗粒细胞凋亡情况，Western Blot 检测 JAK2/STAT3 信号通路有关蛋白表达。 结果 与对照组比较，模型组大鼠卵巢组织病损程度严重、细胞大量丢失、整体结构破坏严重，闭锁卵泡数量 增多、其余各级卵泡数量减少，卵巢系数、性激素（AMH 和 E2）、氧化应激指标（SOD 和 CAT）活性明显降低， MDA和 FSH水平明显提高，卵巢颗粒细胞凋亡比例增多，p-JAK2/JAK2和 p-STAT3/STAT3蛋白表达量明显提 高（P < 0.05）；与模型组比较，随着槲皮素剂量的增加，槲皮素低、中、高剂量组大鼠卵巢组织病损程度明显 减轻、细胞逐渐恢复有序，闭锁卵泡数量减少、其余各级卵泡数量增多，卵巢系数、性激素（AMH和E2）、氧 化应激指标（SOD 和 CAT）活性明显升高，MDA 和 FSH 水平明显降低，卵巢颗粒细胞凋亡比例减少，p-JAK2/ JAK2 和 p-STAT3/STAT3 蛋白表达量明显降低（P < 0.05）；与槲皮素高剂量组比较，槲皮素高剂量＋CA1 组中 CA1可逆转槲皮素对大鼠卵巢损伤的改善作用（P < 0.05）。结论 槲皮素可减轻氧化应激反应、减少细胞凋亡、 改善卵巢组织病损、增强卵巢保护功能，其作用可能与抑制JAK2/STAT3信号通路活性有关。

Objective To investigate the effect of quercetin on improving ovarian function injury in rats with early-onset ovarian insufficiency by regulating JAK2 / STAT3 signaling pathway. Methods The rat model of early-onset ovarian insufficiency was constructed and randomly divided into model group， quercetin low-dose（25 mg · kg-1）group，quercetin medium-dose（50 mg·kg-1）group，quercetin high-dose（100 mg·kg-1）group，quercetin high-dose +JAK2 pathway activator CA1（100 mg·kg-1 quercetin +4 mg·kg-1 CA1）group，with 10 rats in each group. Another 10 healthy rats were selected as control group. The ovarian index， serum levels of follicle-stimulating hormone（FSH）， antiMüllerian hormone（AMH），estradiol（E2），malondialdehyde（MDA），superoxide dismutase（SOD）and catalase （CAT）were detected in all rats. Pathological changes of ovarian tissue and the number of follicles in different stages of development（primary，preantral，antrum，mature and atretic follicles）were observed by HE staining. The apoptosis of ovarian granulosa cells was observed by TUNEL staining and the protein expression of JAK2/STAT3 signaling pathway was detected by Western Blot. Results Compared with the control group， the model group had more severe ovarian lesions. A large number of cells were lost， and the overall structure was destroyed seriously. The number of atretic follicles increased，whereas the number of other follicles decreased. The levels of ovarian index，sex hormones（AMH and E2），oxidative stress indexes（SOD and CAT）decreased significantly，and the levels of MDA and FSH increased significantly. The apoptotic rate of ovarian granulosa cells increased，and the protein expressions of p-JAK2 /JAK2 and p-STAT3 /STAT3 were significantly increased（P < 0.05）. Compared with model group，with the increase of quercetin dose，the degree of ovarian lesion of rats in quercetin low-，medium- and high- dose groups was significantly reduced， cells gradually restored to order，the number of atretic follicles decreased，but the number of other follicles increased. The levels of ovarian index，sex hormone（AMH and E2）and oxidative stress index（SOD and CAT）were significantly increased，the levels of MDA and FSH were significantly decreased，the apoptotic ratio of ovarian granulosa cells was decreased， and the protein expressions of p-JAK2 /JAK2 and p-STAT3 /STAT3 were significantly decreased （P < 0.05）. Compared with quercetin high-dose group， CA1 could reverse the improvement effect of quercetin on ovarian injury in rats with early-onset ovarian insufficiency in quercetin high-dose + CA1 group （P < 0.05）. Conclusion Quercetin can alleviate oxidative stress， reduce cell apoptosis， improve ovarian damage and enhance ovarian protection，which may be related to inhibiting JAK2/STAT3 signaling pathway.

R285.5

国家自然科学基金项目（82104917）