文章摘要
基于Keap-1/Nrf2/HO-1和Caspase-3/Bcl-2/Bax信号通路探讨坤宝丸对早发性卵巢功能不全大鼠的影响
Effects of Kunbao Wan on premature ovarian insufficiency in rats based on Keap-1/Nrf2/HO-1 and Caspase-3/Bcl-2/Bax signaling pathways
投稿时间:2024-10-23  修订日期:2024-10-23
DOI:
中文关键词: 坤宝丸  POI  免疫轴  Keap-1/Nrf2/HO-1  Caspase-3/Bcl-2/Bax
英文关键词: Kunbao Wan  POI  immune axis  Keap-1/Nrf2/HO-1  Caspase-3/Bcl-2/Bax
基金项目:国家重点研发计划项目任务书
作者单位邮编
王婷婷* 北京同仁堂 100071
杨硕 北京同仁堂 
杜菁 北京同仁堂 
王辉 北京同仁堂 
左泽平 北京同仁堂 
徐意 北京同仁堂 
王建芳 北京同仁堂 
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中文摘要:
      目的:探讨坤宝丸对早发性卵巢功能不全(POI)大鼠的治疗作用。方法:采用雷公藤多苷片(TWP)灌胃诱导POI大鼠模型,将大鼠分为空白组、模型组、雌二醇组、坤宝丸低、中、高剂量组,除空白组外,上午灌胃大鼠TWP,连续造模2周,下午灌胃相应药物,连续给药4周。实验结束后,称量大鼠双侧卵巢湿重、子宫、全脑和垂体的重量,计算脏器指数;HE染色观察大鼠卵巢病理的改变,分析卵泡数量的变化;ELISA检测大鼠血清中E2、LH、AMH和FSH含量的变化;IHC分析大鼠卵巢组织中Keap-1、Nrf2、HO-1、Caspase-3、Bcl-2和Bax蛋白阳性表达的情况。结果:与空白组比较,模型组大鼠卵巢湿重、性腺指数、子宫指数和垂体指数明显降低,黄体和闭锁卵泡数量明显增多,原始卵泡、次级卵泡和成熟卵泡明显减少,血清中E2和AMH含量明显降低,LH和FSH含量明显升高,Keap-1、Caspase-3和Bax蛋白阳性表达明显升高,Bcl-2、Nrf2和HO-1蛋白表达明显降低(P < 0.05)。与模型组相比,各给药组卵巢湿重、性腺指数、子宫指数和垂体指数出现不同程度的升高,黄体和闭锁卵泡数量明显减少,原始卵泡、次级卵泡和成熟卵泡明显增多,血清中E2和AMH含量明显升高,LH和FSH含量明显降低,Keap-1、Caspase-3和Bax蛋白阳性表达明显降低,Bcl-2、Nrf2和HO-1蛋白表达量明显升高(P < 0.05)。 结论:坤宝丸对TWP诱导的POI大鼠有一定的治疗作用。其机制可能与影响性激素表达水平和卵泡的发育,调节Keap-1/Nrf2/HO-1和Caspase-3/Bcl-2/Bax通路有关。
英文摘要:
      Objective: To investigate the therapeutic effect of Kunbao Wan on rats with premature ovarian insufficiency. Methods: Tripterygium wilfordii polyglycoside tablets were administered to induce POI rat models, and the rats were divided into blank group, model group, estradiol group, Kunbao Wan low-dose group, Kunbao Wan medium-dose group and Kunbao Wan high-dose group. In addition to the blank group, rats were given TWP intragastric administration in the morning, continuous modeling for 2 weeks, and corresponding drugs were given intragastric administration in the afternoon-4. After the experiment, the wet weight of the ovaries, uterus, whole brain and pituitary gland of the rats were weighed, and the gonadal index and organ index were calculated; HE staining was used to observe the pathological changes of the ovaries of the rats, and the number of original follicles, secondary follicles, mature follicles, corpus luteum and atresia follicles were analyzed; Elisa was used to detect the changes of serum estradiol, luteinizing hormone, anti-Mullerian hormone and follicle-stimulating hormone in rats; IHC was used to analyze the positive expressions of Keap-1 protein, Nrf2 protein, HO-1 protein, Caspase-3 protein, Bcl-2 protein and Bax protein in the ovary tissue of the rats. Results: Compared with the blank group, the ovary wet weight, gonadal index, uterine index and pituitary index of the model group were significantly reduced, the number of luteal and atretic follicles was significantly increased, the original follicle, secondary follicle and mature follicle were significantly reduced, the serum E2 and AMH content was significantly reduced, the LH and FSH content was significantly increased, the positive expression of Keap-1 protein, Caspase-3 protein and Bax protein was significantly increased, the expression of Bcl-2 protein, Nrf2 protein and HO-1 protein was significantly reduced (P < 0.05). Compared with the model group, the ovary wet weight, gonadal index, uterine index and pituitary index in each administration group increased to varying degrees, the number of luteal body and atresia follicles was significantly reduced, the original follicle, secondary follicle and mature follicle were significantly increased, the serum E2 and AMH content was significantly increased, the LH and FSH content was significantly reduced, the positive expression of Keap-1 protein, Caspase-3 protein and Bax protein was significantly reduced, the expression of Bcl-2 protein, Nrf2 protein and HO-1 protein was significantly increased (P < 0.05).
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