两种多囊卵巢综合征动物模型比较及来曲唑诱导的动物模型卵巢组织中血管内皮生长因子和内皮素1的表达  

Comparison of two kinds PCOS animal models and the expression of VEGF and ET-1 in ovarian tissue

作　　者：原振宇[1] 刘梅梅[1] 张艳华[1] 尹晓静[1] 丁慧[1] 刘丽[1] 陈亮[1] 陈天也[1] 

机构地区：[1]哈尔滨医科大学附属第二医院妇产科生殖中心,150086

出　　处：《国际免疫学杂志》2015年第2期124-128,共5页International Journal of Immunology

基　　金：黑龙江省自然科学基金（H201392）

摘　　要：目的比较脱氢表雄酮（DHEA）和来曲唑两种方法诱导的多囊卵巢综合征（PCOS）动物模型哪种更接近临床PCOS，并探讨来曲唑诱导的PCOS动物模型卵巢组织中血管内皮生长因子（VEGF）、内皮素1（ET-1）的表达。方法①通过测量血清激素水平及观察卵巢形态学变化，比较两种PCOS动物模型造模方法的有效性；②筛选较为接近临床PCOS特征的来曲唑造模组并应用免疫组化法检测模型动物卵巢中VEGF、ET-1的表达水平。结果①DHEA组模型与对照组比较，血清睾酮（T）水平轻度升高（（3．147±0．780）ng比（2．221±0．551）ng，P=0．007]，促卵泡生长激素（FSH）水平升高[（6．666±2．260）ng/mL比（4．327±0．949）ng／mL，P=0．011]，雌二醇（E2）[（95．080±9．899）pmol/L比（129．75±17．91）pmol/L，P=0．000]、孕激素（P）[（86．00±8．73）nmol/L比（166．76±30．04）nmol/L，P=0．000]及促黄体生成激素（LH）[（4．188±1．633）mIU／mL比（6．014±1．617）mIU／mL，P=0．022]下降，且模型组卵巢质量及体积低于对照组，模型组镜下可见少量各级卵泡发育及少量成熟卵泡形态，颗粒细胞层减少为5～6层，卵泡膜细胞及间质细胞增生不明显；来曲唑组与对照组比较，血清T明显升高[（15．829±4．103）ng／mL比（7．524±4．208）ng／mL，P=0．000]，LH升高[（8．416±5．629）mIU／mL比（5．629±2．094）mIU／mL，P〈0．05]，且卵巢质量增大，镜下可见多个囊性扩张的卵泡，颗粒细胞层减少为2—3层，卵泡内卵母细胞或放射冠消失。综合血清学变化及卵巢形态变化，来曲唑组大鼠PCOS模型更接近临床PCOS特征；②来曲唑模型动物组卵巢组织中VEGF及ET-1表达均高于对照组（P〈0．05）。结论来曲唑诱导的PCOS大鼠模型更接近临床PCOS，且卵巢组织中VEGF及ET-1呈高表达，二者可能参与PCOS发病机制。Objective To compare the two established rat models induced by dehydroepiandrosterone （DHEA） and letrozole, discuss the expression of vascular edothelial growth factor（VEGF） and endthelin ET-1 of polycystic ovarian syndrome （PCOS） rat model induced by letrozole. Methods （1）By measuring serum level of sex hormone and observing the variation of ovarian morphology, the effectiveness of the two modeling methods was compared;（2）Screening of letrozole made relatively close to the clinical characteristics of PCOS module, immunohistoehemical method was used to detect VEGF and ET-1. Results （~Compared with control group, serum level of testosterone [ （3. 147 ±0. 780） ng vs （2. 221 ± 0.551 ） ng, P = 0. 007 ], follide-stimulating hormone （FSH） [ （ 6. 666 ± 2. 260 ） ng/mL vs （ 4. 327 ± 0. 949 ） ng/mL, P = 0.011 ] were increased, luteinzing hormone （LH） [ （ 4.188 ± 1. 633 ） mlU/mL vs （ 6. 014 ± 1. 617 ） mIU/mL, P = 0. 022 ] estradiol （ E2 ） [ （ 95.08 ± 9. 899 ） pmol/L vs （ 129. 75 ±17.91 ） pmol/L, P = 0. 000 ] and progestogen （ P ） [ （ 86. 00 ± 8. 730 ） nmol/L vs（166.76± 30.04）nmol/L,P = 0. 000 ] were decreased in group DHEA, and the results had statistical significance（P 〈0.05）. In group DHEA, the quality and volume of ovary were significance smaller than those in control, under the microscope, a small amount of follicular at all levels, mature follicle were found, the granular cell layer decreased to 5 ~ 6 layers theca cells and mesenchymal cells were proliferated less obvious . Compared with control group, serum levels of T[ （ 15. 829 ±4. 103 ） ng/mL vs （7. 524 ± 4. 208 ） ng/mL, P = 0. 000 ] and LH [ （ 8.416 ±5. 629 ） mIU/mL vs （ 5. 629 ± 2. 094 ） mIU/mL, P 〈 0.05 ] were significance increased, the ovary mass was also increased in group letrozole. In group letrozole, under the microscope, there were multiple cystic expansion of follicles, the granular cell layer decreased to 2 ~ 3 layers and the oocyte or com

关 键 词：多囊卵巢综合征 血管内皮生长因子 内皮素1 血管生成 

分 类 号：R711.75[医药卫生—妇产科学] R-332[医药卫生—临床医学]