丹那唑对小鼠子宫内膜异位种植的抑制及其机制  

The role of Danazol on the adhesion of ectopic endometrial cells to peritoneum in mice

作　　者：俞而慨[1] 程明军[1] 张晓燕[1] 黄宇婷[1] 邹琴娣[1] 徐丛剑[1] 

机构地区：[1]复旦大学附属妇产科医院中西医结合科,上海200011

出　　处：《复旦学报（医学版）》2008年第5期661-666,共6页Fudan University Journal of Medical Sciences

基　　金：国家自然科学基金项目(30772310);上海市重点学科建设项目(B117)

摘　　要：目的观察丹那唑对子宫内膜异位症模型小鼠异位内膜的影响,以初步探讨子宫内膜异位症中丹那唑对小鼠异位内膜黏附的作用。方法用增强型绿色荧光蛋白(enhanced green fluorescent protein,EGFP)转基因和野生型C57BL/6J小鼠建立子宫内膜异位症模型(n=20),其中丹那唑组(n=10)给予丹那唑灌胃,对照组(n=10)给予等量的生理盐水灌胃。另设空白组(n=5)处理方法同对照组。2周后处死动物,成像并比较两组小鼠荧光表达的强弱;Western blot和real time RT-PCR等技术对异位内膜的黏附因子ICAM-1、CD44进行检测。结果镜下可见模型小鼠肠管间、腹壁下、肝叶下或脾周形成绿色团块状或星点状内膜异位病灶,丹那唑组异位灶体积及荧光表达强度明显低于对照组(P<0.05);丹那唑组和对照组的凋亡率显著高于空白组(P值均<0.001),而丹那唑组的凋亡率显著高于对照组(P<0.01);丹那唑组CD44I、CAM-1蛋白和mRNA表达显著低于对照组(P值均<0.01),以2-△△Ct计算CD44I、CAM-1 mRNA表达量(空白组为1),对照组、丹那唑组的CD44 mRNA表达量分别是空白组的16.34、3.43倍;对照组、丹那唑组的ICAM-1 mRNA表达量分别是空白组的1.53、1.12倍。结论丹那唑可抑制子宫内膜异位症模型小鼠异位内膜的黏附和病灶的产生,这种作用主要可能是通过促进细胞凋亡达到降低黏附因子ICAM-1、CD44的表达而实现的。Objective To evaluate the effect of Danazol on ectopic endometrium of mouse model of endometriosis and to investigate the mechanism and action of it in the adhesion of ectopic endometrial cells to peritoneum. Methods Enhanced green fluorescent protein （EGFP） transgenic and wide-type C57BL/6J mice were used to establish the mouse model （for control or Danazol group, n = 20） of endometriosis. After that sodium chloride was given to the control （n = 10） and blank （n = 5） group, and Danazol was given to Danazol group （n = 10） by gavage per day. Two weeks later all model mice were sacrificed and optical density of fluorescence of ectopic endometrium was calculated. The ectopic endometrium, uterus and ovaries were examined histologically and FCM analysis was performed to access cell apoptosis, Western blot and real time RT-PCR were performed to access the expression of CD44 and ICAM-1 in the ectopic endometrium. Results Under fluorescent microscope the green cake-like or punctiform ectopic endometrium were found between the intestines, under abdominal wall, hepatic lobules or spleen in the model mice of control and Danazol group. The volume and optical density of fluorescence of ectopic endometrium of the control group were significantly higher than that of Danazol group （P〈0.05）. The cell apoptosis of Danazol and control group was significantly higher than that of blank group （P〈0. 001）, and the cell apoptosis of Danazol group was also higher than the control group （P〈0.01）. The expression of CD44 and ICAM-1 in the control and Danazol group was lower than the control group （P〈0.05）. Conclusions Danazol can exert growth-inhibitory effect on ectopic endometrium of model mice. This effect of Danazol might be from apoptosis-inducing to inhibited the expression of CD44 and ICAM-1.

关 键 词：子宫内膜异位症 ICAM-1 CD44 丹那唑 

分 类 号：R711.71[医药卫生—妇产科学]