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目的观察腹腔注射甲氨蝶呤对子宫内膜异位症模型小鼠异位内膜生长的影响,探讨甲氨蝶呤作为难治性子宫内膜异位症治疗药物的可能性。方法2005年6月至2006年5月在复旦大学附属妇产科医院采用增强型绿色荧光蛋白(EGFP)转基因和野生型C57BL/6J小鼠建立子宫内膜异位症模型,2周后对照组(D组)给予等量的生理盐水腹腔注射,实验组分别给予25mg/kg(A组),50mg/kg(B组),75mg/kg(C组)的甲氨蝶呤腹腔注射,1周后处死动物,荧光活体成像后比较各组小鼠荧光表达的强弱,取异位病灶、子宫及卵巢行病理检测,流式细胞术检测异位病灶的凋亡情况。结果镜下可见模型小鼠肠管间、腹壁下、肝小叶下或脾周形成绿色团块状或星点状内膜异位病灶,实验组异位灶体积及荧光表达强度明显低于对照组(P<0.01),而各实验组异位内膜细胞凋亡率明显高于对照组(P<0.05),且这种差别呈剂量依赖(P<0.05)。结论甲氨蝶呤可抑制子宫内膜异位症模型小鼠异位内膜细胞的生长并诱导其凋亡,且这种作用呈剂量依赖,提示肿瘤化疗药甲氨蝶呤有望用于某些难治性子宫内膜异位症的临床治疗。
Objective To observe the effect of methotrexate intraperitoneal injection on ectopic endometrial growth in endometriosis model mice and to explore the possibility of methotrexate as refractory endometriosis treatment drug. Methods From June 2005 to May 2006, the model of endometriosis was established by enhanced green fluorescent protein (EGFP) transgenic and wild-type C57BL / 6J mice in the Obstetrics and Gynecology Hospital of Fudan University. Two weeks later, the control group (Group D) were injected intraperitoneally with the same volume of saline. The experimental group were given intraperitoneal injection of methotrexate 25mg / kg (group A), 50mg / kg (group B) and 75mg / kg (group C) The animals were sacrificed, and the fluorescence intensity of the mice in each group was compared after imaging. The ectopic lesions, uterus and ovary pathological examination were performed. The apoptosis of ectopic lesions was detected by flow cytometry. Results Microscopic or star-shaped endometriotic lesions were formed in the intestine, abdominal wall, hepatic lobule or spleen of the model mice. The volume and the intensity of ectopic focus in the experimental group were significantly lower than those in the control group P <0.01). The apoptosis rate of ectopic endometrial cells in each experimental group was significantly higher than that in the control group (P <0.05), and the difference was dose-dependent (P <0.05). Conclusion Methotrexate can inhibit the growth and induce the apoptosis of ectopic endometrial cells in endometriosis mice in a dose-dependent manner, suggesting that the chemotherapeutic agent methotrexate is expected to be used in some Clinical treatment of refractory endometriosis.