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江雪娟,陈晓菲,俞佳,王晨晔,胡慧敏,丁彩飞.槲皮素改善多囊卵巢综合征大鼠胰岛素抵抗和卵泡发育的作用机理研究[J].浙江中西医结合杂志,2024,34(10):
槲皮素改善多囊卵巢综合征大鼠胰岛素抵抗和卵泡发育的作用机理研究
Effect of quercetin on insulin resistance and follicular development in rats with polycystic ovary syndrome
投稿时间:2024-04-30  修订日期:2024-08-16
DOI:
中文关键词:  槲皮素  多囊卵巢综合征  卵泡  AGEs/RAGE
英文关键词:Quercetin  polycystic ovary syndrome  follicles  AGEs/RAGE
基金项目:杭州市卫生科技计划项目(ZD20200016;ZD20210029;OO2019011;OO2019008); 浙江省中医药科学研究B类(2021ZB210);杭州市红十字会医院院内科研基金(HHQN2021005);浙江省自然科学(LQ19H270005)
作者单位E-mail
江雪娟 浙江省中西医结合医院 Jiangxuejuan88@163.com 
陈晓菲   
俞佳   
王晨晔   
胡慧敏   
丁彩飞* 浙江省中西医结合医院 dingcaifei@163.com 
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中文摘要:
      目的:探究槲皮素(Quercetin, Q)是否通过AGEs/RAGE代谢通路改善多囊卵巢综合征(polycystic ovarian syndrome,PCOS)大鼠胰岛素抵抗(Insulin resistance, IR)和卵泡发育。方法:30只SD大鼠随机平均分为Control、PCOS、PCOS +L-Q(15 mg/kg)、PCOS+H-Q(30 mg/kg)和PCOS+MH阳性对照组。来曲唑联合高脂饲料建立大鼠PCOS模型,给予相应药物干预四周。随后测定空腹血糖(FPG)及胰岛素水平(FINS)并计算胰岛素抵抗(HOMA-IR),对大鼠行阴道涂片观察动情周期变化,ELISA检测雌二醇E2、孕酮P、促卵泡生成素FSH、黄体生成素LH、雄激素T水平,HE观察卵巢组织病理变化,TUNEL检测卵巢组织细胞凋亡情况,免疫组化及Western blot测定AGEs/RAGE通路及凋亡相关蛋白表达情况。结果:与PCOS组相比,PCOS+H-Q组和PCOS+MH组大鼠FPG、FINS、HOMA-IR,血清中E2、LH、T以及卵巢组织中AGEs、RAGE、cleaved-Caspase3和Bax蛋白的表达水平均显著降低,血清中P及卵巢组织中Bcl-2蛋白的表达水平显著升高(P<0.05或P<0.01)。阴道涂片及HE染色结果显示槲皮素及MH治疗后,大鼠出现完整动情周期且卵巢颗粒细胞及优势卵泡增多,同时细胞凋亡率显著降低。结论:槲皮素能够促进PCOS大鼠卵泡发育,抑制大鼠卵巢细胞凋亡及IR,其可能与降低AGEs/RAGE代谢通路活性和调控凋亡相关信号通路有关。
英文摘要:
      【Objective】This study aim to investigate whether Quercetin (Q) can improve insulin resistance (IR) and follicular development in rats with polycystic ovarian syndrome (PCOS) through AGEs/RAGE metabolic pathway. 【Methods】Thirty SD rats were randomly divided into Control, PCOS, PCOS+ L-Q (15 mg/kg), PCOS+H-Q (30 mg/kg) and PCOS+MH positive Control group. Rat PCOS model was established by letrozole combined with high fat diet, and corresponding drugs were administered for four weeks. Fasting blood glucose (FPG) and insulin levels (FINS) were measured and insulin resistance (HOMA-IR) was calculated. Vaginal smear was performed to observe the changes of estrus cycle. Estradiol E2, progesterone P, follicle-stimulating hormone FSH, luteinizing hormone LH and androgen T were detected by ELISA. TUNEL was used to detect the apoptosis of ovarian tissues, and the expression of AGEs/RAGE pathway and apoptosis-related proteins was determined by immunohistochemistry and Western blot. 【Results】Compared with the PCOS group, FPG, FINS, HOMA-IR, E2, LH, T levels in serum and AGEs, RAGE, Cleaved Caspase3 and Bax protein levels in ovarian tissues of PCOS+H-Q group and PCOS+MH group were significantly decreased. The expression levels of P in serum and Bcl-2 protein in ovarian tissue were significantly increased (P<0.05 or P<0.01). The results of vaginal smear and HE staining showed that after quercetin and MH treatment, the rats had a complete estrus cycle, and the number of granulosa cells and dominant follicles increased, and the cell apoptosis rate decreased significantly. Conclusion: Quercetin can promote follicular development in PCOS rats, inhibit apoptosis and IR of rat ovarian cells, which may be related to reducing the activity of AGEs/RAGE metabolic pathway and regulating apoptosis related signaling pathway. 【Conclusion】Quercetin can promote follicular development in PCOS rats and inhibit apoptosis and IR of rat ovarian cells, which may be related to reducing the activity of AGEs/RAGE metabolic pathway and regulating apoptosis related signaling pathway.
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