DNA甲基化在子宫内膜异位症发病机制中的作用及地西他滨对其治疗的研究

目的探讨DNA甲基化在子宫内膜异位症发病机制中的作用以及DNA甲基转移酶抑制剂地西他滨在内异症治疗中的可行性。方法根据大鼠自体移植方法构建大鼠子宫内膜异位症模型,4周后2次开腹判断造模是否成功,用游标卡尺测量记录异位灶体积后将大鼠随机分为实验组(12只)、PBS组(12只)和对照组(11只)。同时选取未造模的正常大鼠作为空白组(10只)。实验组大鼠腹腔注射5-氮-2’-脱氧胞苷(2.5 mg/kg/d),PBS组注射等量PBS溶液,对照组未用药。应用免疫组织化学染色方法和Western Blot法检测各组异位灶内DNA甲基转移酶1的表达情况。收集腹腔冲洗液用Elisa法检测肿瘤坏死因子(tumor necrosis factor-α,TNF-α)含量。结果 50只大鼠根据大鼠子宫内膜自体移植方法成功35只,造模成功率为70%(35/50)。实验组大鼠经药物处理后异位灶体积明显缩小(P0.05),PBS组及对照组异位灶体积无明显改变(P0.05)。实验组用药后异位内膜组织上皮细胞体积缩小,腺体萎缩,囊液分泌减少;异位灶组织中DNA甲基转移酶1的表达低于PBS组及对照组(P0.05),PBS组及对照组间表达无明显差异(P0.05)。治疗后实验组大鼠腹腔冲洗液中TNF-α含量较PBS组及对照组降低,造模组(实验组、PBS组、对照组)较空白组均升高(P0.05)。结论 DNA甲基转移酶抑制剂能明显缩小异位灶体积,促进异位灶萎缩。DNA甲基转移酶抑制剂能抑制异位灶中DNA甲基转移酶表达,这可能是其抑制病灶生长的途径之一。DNA甲基转移酶抑制剂能抑制子宫内膜异位症大鼠模型腹腔环境中TNF-α的含量。

The role of DNA methylation in the pathogenesis of endometriosis and the study of decitabine in treating endometriosis

Objective To investigate the role of DNA methylation in the pathogenesis of endometriosis and the possibility of dicetaxine,a DNA methyltransferase inhibitor,in the treatment of endometriosis.Methods Rat models of endometriosis were established by autologous transplantation.After 4 weeks,determined whether the success of modeling 2 times,measured ectopic stove volume with a vernier caliper.The rats were randomly divided into experimental group (n =12),PBS group (n =12) and control group (n=11).At the same time,normal rats without modeling were selected as blank group (n =10).In the experimental group,5-aza-2'-deoxycytidine (2.5mg / kg / d) was injected intraperitoneally.PBS solution was injected into the PBS group,but not in the control group.The expression of DNA methyltransferase 1 in ectopic endometrium was detected by immunohistochemical staining and Western Blot.The content of tumor necrosis factor (TNF-α) was measured by Elisa method.Results Thirty-five rats were successfully established by autologous transplantation of endometrium.The success rate of model establishment was 70%(35/50).The volume of ectopic foci in the experimental group decreased significantly (P<0.05),but there was no significant difference between the PBS group and the control group (P> 0.05).In the experimental group,the volume of ectopic endometrial epithelial cells decreased,glandular atrophy and cyst fluid secretion were decreased.The expression of DNA methyltransferase-1 in ectopic foci of experimental group was significantly lower than that in PBS group and control group (P<0.05).There was no significant difference between PBS group and control group.The content of TNF-α in the peritoneal lavage fluid of the experimental group was lower than that of the PBS group and the control group (P<0.05).The level of TNF-α in the experimental group was significantly higher than that in the PBS group and control group (P< 0.05).Conclusion DNA methyltransferase inhibitor can significantly reduce the volume of ectopic foci and promote ectopic atrophy.DNA methyltransferase inhibitors can inhibit the expression of DNA methyltransferase in ectopic foci,which may be one of the ways to inhibit the growth of lesions.DNA methyltransferase inhibitor can inhibit the content of TNF-α in the abdominal cavity of rats with endometriosis.