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基于MAPK/CREB信号通路探讨南珠蜂蜜液对围绝经期综合征大鼠的影响

Effects of Nanzhu Honey Liquid on a rat model of perimenopausal syndrome via MAPK/CREB signaling pathway
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摘要 目的 探讨南珠蜂蜜液改善围绝经期综合征大鼠症状的作用。方法 采用双侧卵巢切除术建立围绝经期综合征大鼠模型,随机分为假手术组、模型组、坤泰胶囊组(0.63 g/kg)和南珠蜂蜜液低、中、高剂量组(0.031 5、0.063、0.126 g/kg),连续干预15 d。HE染色观察子宫组织形态学变化和动情周期变化;ELISA法检测血清雌二醇(E_(2))、卵泡刺激素(FSH)和黄体生成素(LH)水平;RT-qPCR法检测子宫和下丘脑组织ERα、MAP2K1、ERK1/2、CREB mRNA表达;Western blot法检测下丘脑组织ERK信号通路关键蛋白表达。结果 与假手术组比较,模型组大鼠子宫和下丘脑系数降低(P<0.01);血清E_(2)水平降低(P<0.01),FSH和LH水平升高(P<0.05,P<0.01);子宫组织结构紊乱,内膜上皮细胞低柱状改变,固有层腺体数量减少,毛细血管分布稀疏;子宫和下丘脑组织ERα、MAP2K1、ERK1/2(p-ERK)和CREB(p-CREB)mRNA及蛋白表达均降低(P<0.01)。与模型组比较,坤泰胶囊组和南珠蜂蜜液高剂量组大鼠子宫和下丘脑系数升高(P<0.05,P<0.01);血清E_(2)水平升高(P<0.05,P<0.01),FSH和LH水平降低(P<0.05,P<0.01);子宫组织结构明显改善,管径增粗、内膜增厚、上皮细胞恢复单层柱状排列,固有层腺体数量增加并可见新生毛细血管;子宫和下丘脑组织ERα、MAP2K1、ERK1/2(p-ERK)和CREB(p-CREB)mRNA及蛋白表达升高(P<0.05,P<0.01)。结论 南珠蜂蜜液可能通过上调MAP2K1、ERK和CREB表达,激活MAPK信号通路,从而改善围绝经期综合征大鼠的性激素水平,修复子宫和下丘脑组织的病理损伤。 AIM To investigate the effects of Nanzhu Honey Liquid on symptoms improvement in a rat model of perimenopausal syndrome.METHODS With the rat models of perimenopausal syndrome established by bilateral ovariectomy,rats were randomly divided into the sham operation group,the model group,the Kuntai Capsule group(0.63 g/kg)and the low-dose,medium-dose and high-dose Nanzhu Honey Liquid groups(0.0315,0.063 and 0.126 g/kg),for 15 days respective drug administration.HE staining was employed to assess uterine tissue morphology and estrous cycle alteration.Serum levels of estradiol(E_(2)),follicle stimulating hormone(FSH)and luteinizing hormone(LH)were quantified using ELISA.RT-qPCR measured mRNA expressions of ERα,MAP2K1,ERK 1/2 and CREB in both uterus and hypothalamic tissues.Western blot further examined key protein expressions within the ERK signaling pathway in the hypothalamus.RESULTS Compared to the sham operation group,the model group showed significant reductions in uterine and hypothalamic indices(P<0.01);markedly decreased serum E_(2) level(P<0.01),elevated FSH and LH levels(P<0.05,P<0.01);disorganized uterine tissue architecture,atrophic endometrial epithelium with reduced glandular density in the lamina propria,and sparse capillary distribution;and downregulated mRNA and protein expressions of ERα,MAP2K1,ERK1/2(p-ERK)and CREB(p-CREB)in uterus and hypothalamus(P<0.01).Compared to the model group,the groups treated with Kuntai Capsule or high-dose Nanzhu Honey Liquid exhibited significantly increased uterine and hypothalamic indices(P<0.05,P<0.01);elevated serum E_(2) level(P<0.05,P<0.01)and reduced FSH and LH levels(P<0.05,P<0.01);restored uterine architecture with increased endometrial thickness,transition to single-layer columnar epithelium,enhanced glandular density in the lamina propria,and formation of new capillaries;and increased mRNA and protein expressions of ERα,MAP2K1,ERK1/2(p-ERK)and CREB(p-CREB)in both uterus and hypothalamus(P<0.05,P<0.01).CONCLUSION Nanzhu Honey Liquid may activate MAPK signaling pathway by up-regulating the expressions of MAP2K1,ERK and CREB,thereby enhancing sex hormone levels in rats with perimenopausal syndrome and mitigating the pathological damage of the uterus and hypothalamus.
作者 邓亚胜 梁天薇 黄慧 范燕萍 郑艺清 刘永辉 倪召兵 陈秋 黄语嫣 林江 DENG Ya-sheng;LIANG Tian-wei;HUANG Hui;FAN Yan-ping;ZHENG Yi-qing;LIU Yong-hui;NI Zhao-bing;CHEN Qiu;HUANG Yu-yan;LIN Jiang(Guangxi University of Chinese Medicine,Nanning 530200,China;The Affiliated Hospital of Chengdu University of Traditional Chinese Medicine,Chengdu 610075,China;Fangchenggang Hospital of Traditional Chinese Medicine,Fangchenggang 538000,China)
出处 《中成药》 北大核心 2025年第12期3968-3975,共8页 Chinese Traditional Patent Medicine
基金 广西自然科学基金项目(2025GXNSFDA069048) 全国高校黄大年式教师团队“中西医基础课程教师团队”项目(教育部教师函[2022]2号) 广西名中医林江传承工作室项目(桂中医药科教发[2021]6号) 中医学广西一流学科项目(桂教科研[2022]1号) 广西中医药多学科交叉创新团队项目(GZKJ2302)。
关键词 南珠蜂蜜液 围绝经期综合征 下丘脑 性激素 ERα MAPK/CREB信号通路 Nanzhu Honey Liquid perimenopausal syndrome hypothalamus sex hormones ERα MAPK/CREB signaling pathway
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