【摘要】 目的 探讨二甲双胍在改善氧化应激损伤卵巢功能低下小鼠卵巢储备中的作用及NLRP1等炎症小体可能的作用机制。方法 通过雷公藤多苷建立氧化应激损伤早发性卵巢功能不全小鼠模型,并通过二甲双胍干预模型组与正常对照组小鼠,从动情周期、卵巢指数、各级卵泡计数和血清激素水平等方面,评估二甲双胍对卵巢功能的改善作用;采用ELISA检测小鼠血清激素水平,微板法检测血清氧化应激水平,Western blot检测卵巢组织NLRP1炎症小体、NLRP3、NF-κB、NLRP12、IL-1β和IL-18在二甲双胍改善卵巢储备过程中的表达情况。结果 雷公藤多苷成功诱导氧化应激损伤早发性卵巢功能不全小鼠模型建立;二甲双胍可以缩短模型小鼠动情间期,延长动情期,升高卵巢指数,提高原始卵泡、窦前卵泡、窦状卵泡、成熟卵泡和黄体数量,降低闭锁卵泡数量;二甲双胍干预模型组血清促卵泡生成素水平下降,雌二醇、抗苗勒管激素升高,抗氧化指标升高,氧化指标降低,NLRP1、NLRP3、NF-κB及IL-1β和IL-18表达下调,NLRP12表达上调。结论 二甲双胍具有抗氧化应激作用,可能通过抑制NLRP1等炎症小体复合物的激活改善卵巢功能。更多还原

【Abstract】 Objective To explore the role of metformin in improving ovarian reserve in mice with ovarian dysfunction induced by oxidative stress and the possible mechanism of inflammasomes such as NLRP1.Methods The mouse model of premature ovarian insufficiency induced by oxidative stress was established by tripterygium glycosides,and the mice in the model group and the normal control group were treated by metformin.The effect of metformin on the improvement of ovarian function was evaluated according to estrous cycle,ovarian index,follicle count at all levels and serum hormone level.ELISA was used to detect serum hormone levels in mice,microplate method was used to detect serum oxidative stress levels,and Western blot was used to detect the expression of NLRP1 and other inflammasomes,NLRP3,NF-κB,NLRP12,IL-1 β and IL-18 in ovarian tissue during the process of improving ovarian reserve with metformin.Results Tripterygium glycosides induced successfully the mouse model of premature ovarian insufficiency induced by oxidative stress.Metformin could shorten the estrous period,prolong the estrus period,increase the ovarian index,increase the number of primordial follicles,preantral follicles,antral follicles,mature follicles and corpus luteum,and reduce the number of atretic follicles of the model mice.In the model group,serum follicle-stimulating hormone levels decreased,estradiol and anti-Müllerian hormone increased,antioxidant indexes increased,oxidation indexes decreased;the expressions of NLRP1,NLRP3,NF-κB,IL-1 β,and IL-18 were down-regulated and NLRP12 expression was up-regulated.Conclusion Metformin has anti-oxidative stress effects and may improve ovarian function by inhibiting the activation of inflammasome complexes such as NLRP1.更多还原