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

作　　者：王婷婷 杨硕 杜菁 王辉 左泽平 徐意 王建芳[3] WANG Ting-ting;YANG Shuo;DU Jing;WANG Hui;ZUO Ze-ping;XU Yi;WANG Jian-fang(Department of Innovation Development,China Bejing Tongrentang Group Co.,Ltd.Beijing,100079,China;Center for Drug Safety Evaluation,Beijing Tong Ren Tang joint stock company,Beijing,100079,China;Department of Gastroenterology,Beijing University of Chinese Medicine Oriental Hospital,Beijing,100078,China)

机构地区：[1]中国北京同仁堂(集团)有限责任公司创新发展部,北京100079 [2]北京同仁堂股份有限公司科学研究所药物安全评价中心,北京100079 [3]北京中医药大学东方医院消化内科,北京100078

出　　处：《现代生物医学进展》2025年第4期601-611,共11页Progress in Modern Biomedicine

基　　金：国家重点研发计划项目(2019YFC1711400)。

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(TWP)片灌胃诱导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E_(2)、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E_(2)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E_(2)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。Objective:To investigate the therapeutic effect of Kunbao Wan on rats with premature ovarian insufficiency.Methods:Tripterygium wilfordii polyglycoside tablets were administered to induce rat models of premature ovarian insufficiency,and the rats were divided into control group,model group,positive group,Kunbao Wan low-dose group,Kunbao Wan medium-dose group and Kunbao Wan high-dose group.In addition to the control group,rats were given tripterygium wilfordii Polyglycosides intragastric administration in the morning,continuous modeling for 2 weeks,and corresponding drugs were given intragastric administration in the afternoon among 4 weeks.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;Hematoxylin-eosin staining 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;Enzyme linked immunosorbent assay was used to detect the changes of serum estradiol,luteinizing hormone,anti-Mullerian hormone and follicle-stimulating hormone in rats;Immunohistochemistry was used to analyze the positive expressions of Keap-l 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 control 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 E_(2) 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

关 键 词：坤宝丸 POI 免疫轴 Keap-1/Nrf2/HO-1 Caspase-3/Bcl-2/Bax 

分 类 号：R3[医药卫生—基础医学] R285.5