不同造模时长对来曲唑诱导的多囊卵巢综合征大鼠肠道菌群的影响  

Effect of different modeling time on intestinal bacteria in letrozole induced PCOS rats

作　　者：贾凡 郑冬雪 陈如枫 赵红玉 刘津源 张莉莉[1] 赵林华[1] 刘咏梅[1] 张云[1] 朱晓云[1] 阚杰[1] 刘新敏[1] JIA Fan;ZHENG Dong-xue;CHEN Ru-feng;ZHAO Hong-yu;LIU Jin-yuan;ZHANG Li-li;ZHAO Lin-hua;LIU Yong-mei;ZHANG Yun;ZHU Xiao-yun;KAN Jie;LIU Xin-min(Guang’anmen Hospital,China Academy of Chinese Medical Sciences,Beijing 100053,China)

机构地区：[1]中国中医科学院广安门医院,北京100053

出　　处：《海南医学院学报》2022年第2期81-91,共11页Journal of Hainan Medical University

基　　金：国家自然科学基金项目(81674011)。

摘　　要：目的:比较不同造模时长下,来曲唑诱导的多囊卵巢综合征(polycystic ovary syndrome,PCOS)大鼠卵巢形态学、生殖激素、糖脂代谢水平及肠道菌群等的差异。方法:采用随机数字表法,将18只21日龄SPF级雌性SD大鼠随机分为A组(造模3周组)、B组(造模5周组)、D组(对照组)。A组前3周予来曲唑+CMC-Na混合液、后2周予CMC-Na溶液灌胃,B组予来曲唑+CMC-Na混合液灌胃5周,D组予CMC-Na溶液灌胃5周,3组大鼠均予普通饲料饲养。灌胃结束后观察各组大鼠的体质量、苏木素-伊红(H&E)染色法观察卵巢组织学变化,酶联免疫吸附法(ELISA)法检测大鼠血清雌二醇(estradiol,E_(2))、卵泡刺激素(follicle stimulating hormone,FSH)、黄体生成素(luteinizing hormone,LH)、睾酮(testosterone,T)、总胆固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)、空腹胰岛素(fasting insulin,FINS)及脂多糖(lipopolysaccharide,LPS)等水平,使用血糖仪检测大鼠空腹血糖(Glu),计算LH/FSH比值和胰岛素抵抗指数(homeostasis model of assessment for insulin resistence index,HOMA IR);采用16S rRNA技术检测大鼠的肠道菌群。结果:(1)卵巢组织形态学比较:光镜下,D组可见多个黄体,成熟卵泡内可见卵母细胞,颗粒细胞排列整齐并呈多层,无囊状扩张卵泡;A、B组卵巢组织无发育成熟的卵泡,卵泡结构不规则并可见较多的囊状扩张卵泡,部分卵泡颗粒细胞层数减少甚至消失。(2)性激素水平比较:与D组相比,B组T水平明显升高(P<0.001),A组T水平有上升趋势(P>0.05);A、B组LH/FSH水平均明显升高(P<0.001)。与A组相比,B组E_(2)显著降低(P<0.05),T显著升高(P<0.01)。(3)糖、脂代谢水平比较:与D组相比,A、B组TC水平明显升高(P<0.01)。与A组相比,B组TG显著升高(P<0.05)。各组大鼠Glu、FINS、HOMA-IR水平无显著差异。(4)LPS水平比较:与D组相比,A、B组大鼠血清LPS水平明显上升(P<0.001)。(5)肠道菌群分析比较:门水平上,与D组相比,B组�Objective:To compare the differences in ovarian morphology,reproductive hormones,glucose and lipid metabolism level and intestinal flora of polycystic ovary syndrome(PCOS)rats induced by letrozole under different modeling time.Methods:Eighteen 21-day SPF female SD rats were randomly divided into the group A(3-week group),the group B(5-week group)and the group D(control group)by random number table method.Group A received letrozole+CMC-Na mixture by gavage in the first 3 weeks and CMC-Na solution by gavage in the last 2 weeks,group B received letrozole+CMC-Na mixture by gavage for 5 weeks,and group D received CMC-Na solution by gavage for 5 weeks,and all three groups of rats were fed with a normal diet.At the end of gavage,the body weight of rats in each group was observed,the histological changes of ovaries were observed by hematoxylin-eosin(HE)staining,the serum levels of estradiol(E_(2)),follicle stimulating hormone(FSH),luteinizing hormone(LH),testosterone(T),total cholesterol(TC),triglyceride(TG),fasting insulin(FINS)and lipopolysaccharide(LPS)were measured by enzymelinked immunosorbent assay(ELISA),fasting blood glucose(Glu)of rats was measured by a glucose meter,and the LH/FSH ratio and insulin resistance index(HOMA IR)were calculated;the intestinal bacteria of rats were detected by 16S rRNA technique.Re⁃sults:Under light microscope,multiple luteum and oocytes were observed in mature follicles in the group D,and granulosa cells were orderly arranged and multilayered,without cystic dilated follicles.There were no mature follicles in the ovarian tissues of group A and group B.The follicles were irregular in structure and more cystic dilated follicles were visible.The number of granular cells in some follicles decreased or even disappeared.Compared with group D,T level in the group B was significantly increased(P<0.001),and T level in the group A had an upward trend(P>0.05);the LH/FSH levels in group A and B were significantly increased(P<0.001).Compared with the group A,E_(2) in the group B was significantl

关 键 词：多囊卵巢综合征 来曲唑 造模 肠道菌群 

分 类 号：R711.75[医药卫生—妇产科学]