刘冉冉 骆倩倩 孙晓娟

[摘要] 目的 建立多囊卵巢综合征（PCOS）大鼠模型，探讨卵巢组织中kisspeptin/kiss1r系统表达及作用。 方法 孕10 d的Wistar大鼠20只，其雌性后代60只，根据随機数字表法分为PCOS组和正常组，每组30只。PCOS组给予来曲唑和羧甲基纤维素（CMC）连续灌胃21 d，正常组给予等体积的CMC灌胃。造模结束后检测两组大鼠体重参数和血清激素水平;HE染色检测卵巢组织形态学改变;免疫组织化学染色和qRT-PCR检测卵巢组织中kisspeptin和kiss1r的表达。 结果 与正常组比较，PCOS组大鼠的体重、腹膜后脂肪含量、卵巢重量均增加，血清黄体生成素、卵泡刺激素和睾酮水平均升高（P < 0.05或P < 0.01）。与正常组比较，PCOS组大鼠卵巢中kiss1-mRNA表达降低（P < 0.05）;两组大鼠卵巢中kiss1r-mRNA表达比较，差异无统计学意义（P > 0.05）。PCOS组大鼠卵巢具有典型的多囊样改变。 结论 PCOS大鼠卵巢可见kisspeptin/kiss1r系统的低表达，可能在PCOS的发生、发展中起重要作用。

[关键词] 多囊卵巢综合征;Kisspeptin/kiss1r系统;卵巢;来曲唑

[中图分类号] R711.75          [文献标识码] A          [文章编号] 1673-7210（2020）07（a）-0016-04

[Abstract] Objective To establish a rat model of polycystic ovary syndrome （PCOS） and investigate the expression and function of kisspeptin/kiss1r system in ovarian tissue. Methods Twenty Wistar rats at the 10th day of gestation were divided into PCOS group and normal group according to the random number table method， with 30 rats in each group. In PCOS group， Letrozole and carboxy methyl cellulose （CMC） were administered continuously for 21 days， while in normal group， CMC of equal volume was administered. Body weight parameters and serum hormone levels of two groups were measured after model establishment; the ovarian histomorphology was detected by HE staining; the expression of kisspeptin and kiss1r in the ovarian tissue was detected by immunohistochemistry and qRT-PCR. Results Compared with normal group， the weight， the content of retroperitoneal fat and the weight of ovary in PCOS group were increased， and the levels of serum luteinizing hormone， follicle stimulating hormone and testosterone were increased （P < 0.05 or P < 0.01）. Compared with normal group， the expression of kiss1-mRNA in the ovaries of PCOS group was decreased （P < 0.05）. There was no significant difference in kiss1r-mRNA expression between two groups （P > 0.05）. PCOS group showed typical polycystic changes in ovaries. Conclusion Down-regulation of kisspeptin/kiss1r system in the ovaries of PCOS rats may play an important role in the occurrence and development of PCOS.

[Key words] Polycystic ovarian syndrome; Kisspeptin/kiss1r system; Ovary; Letrozole

多囊卵巢综合征（PCOS）是临床上最常见的内分泌紊乱性疾病，多伴有卵泡发育异常和雄激素增多[1]，造成闭经、不育、多毛、肥胖等[2]。由于发病率高，治疗困难，增加肿瘤[3]的发生，PCOS成为重要的研究课题。目前对PCOS病因的研究较多，大多与下丘脑-垂体-性腺轴有关。kisspeptin/kiss1受体（kiss1r）系统是此轴最强有力的影响因素[4]。kisspeptin是由kiss1基因编码的神经肽前体，可以结合并激活其受体kiss1r，并发挥作用。食源性肥胖大鼠下丘脑中的kisspeptin表达减少[5]，导致生殖障碍，营养不良、糖尿病等均会引起下丘脑kisspeptin/kiss1r系统的异常表达[6]。在PCOS大鼠中，下丘脑kiss1基因和kisspeptin表达均有显著改变[7-8]。本研究主要探究kisspeptin/kiss1r系统在多囊卵巢中的作用，以了解其发病机制。……