摘要
目的探讨槲皮素是否通过介导细胞外信号调节激酶(ERK1/2)信号通路对特发性中枢性性早熟产生影响,明确槲皮素干预特发性中枢性性早熟的相关作用机制。方法将48只15日龄SPF健康C57BL/6J雌性小鼠随机分为空白对照组、ICPP模型组、亮丙瑞林组、槲皮素干预组,每组12只。造模成功后记录集各组雌鼠阴门开启时间,观察各组雌鼠阴道上皮细胞表现,采用酶联免疫吸附法测定各组雌鼠血清激素相关指标,采用免疫组织化学染色法观察各组雌鼠下丘脑GnRH表达情况,采用RT-PCR技术和蛋白免疫印迹法检测各组雌鼠下丘脑中GnRH、Kiss-1、GPR54、ERK1/2信号通路mRNA和蛋白表达。结果与空白对照组相比,ICPP模型组雌鼠阴门开启时间明显提前(P<0.001),ICPP模型组雌鼠血清FSH、E_(2)、LH明显升高(P均<0.001);经亮丙瑞林和槲皮素干预后,ICPP模型雌鼠的阴门开启时间得到了明显延长(P<0.001),ICPP模型雌鼠的雌激素分泌活性均得到明显抑制(P均<0.05);且槲皮素抑制效果明显优于亮丙瑞林组且槲皮素干预效果明显优于亮丙瑞林组(P均<0.001)。与空白对照组相比,ICPP模型组雌鼠GnRH蛋白光密度值明显升高(P<0.001);ICPP雌鼠经亮丙瑞林/槲皮素干预后下丘脑中GnRH、Kiss-1、GPR54、ERK1/2信号通路mRNA和蛋白基因表达均得到明显抑制(P<0.001)。结论槲皮素可通过下调ERK1/2信号通路相关蛋白表达,抑制这一信号途径,进而对Kiss-1、GPR54 mRNA表达起到抑制效应,降低下丘脑-垂体-性腺轴活性,进而调节ICPP血清雌激素浓度,发挥延缓ICPP的效用。
Objective To investigate whether quercetin influences idiopathic central precocious puberty by mediating Extracellular signal-regulated kin-1 and-2(ERK1/2)signaling pathway,and to clarify the relevant mechanism of quercetin's intervention in idiopathic central precocious puberty.Methods 15-day-old SPF healthy C57BL/6J female mice were selected as experimental subjects and randomly divided into blank control group,ICPP model group,leprerelin group and quercetin intervention group,with 12 mice in each group.After the model was successfully constructed,the opening time of the pubic door of female mice in each group was recorded,and the expression of vaginal epithelial cells of female mice in each group was observed.The serum hormone related indexes of female mice in each group were determined by enzyme-linked immunosorbent assay,and the expression of GnRH in the hypothalamus of female mice was observed by immunohistochemical staining.The mRNA and protein expressions of GnRH,Kiss-1,GPR54 and ERK1/2 signaling pathways in the hypothalamus of female rats were detected by RT-PCR and Western blot.Results Compared with the blank control group,the vaginal opening time of female rats in the ICPP model group was significantly earlier(P<0.001),and the serum FSH,E2 and LH of female rats in the ICPP model group increased significantly(all P<0.001).After the intervention of leuprolide and quercetin,the vaginal opening time of female rats in ICPP model was significantly prolonged(P<0.001),and the estrogen secretion activity of female rats in ICPP model was significantly inhibited(all P<0.05).The inhibitory effect of quercetin was significantly better than leuprolide group and the intervention effect of quercetin was significantly better than leuprolide group(all P<0.001).Compared with the blank control group,the optical density of GnRH protein in the ICPP model group was significantly increased(P<0.001).The mRNA and protein expressions of GnRH,Kiss-1,GPR54 and erk1/2 signaling pathways in hypothalamus of ICPP female rats were significantly inhibited after leuproline/quercetin intervention(P<0.001).Conclusion Quercetin can inhibit the mRNA expression of Kiss-1 and GPR54 by down-regulating the expression of signal pathwage-related proteins in ERK1/2 signaling pathway,and then inhibit the mRNA expression of Kiss-l and GPR54,reduce the activity of hypothalamic-pituitary-gonadal axis,and then regulate the serum estrogen concentration of ICPP,thus delaying ICPP.
作者
胡红
周惠
代静
HU Hong;ZHOU Hui;DAI Jing(Pediatrics Department,Zigong Third People's Hospital,Zigong,Sichuan 643000,China)
出处
《中国优生与遗传杂志》
2025年第9期1908-1912,共5页
Chinese Journal of Birth Health & Heredity
基金
2021年四川省医学(青年创新)科研项目(S21150)。
