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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(P<0.05),PBS组及对照组异位灶体积无明显改变(P>0.05)。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(P<0.05),PBS组及对照组间表达无明显差异(P>0.05)。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(P<0.05)。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。
Objective To investigate the role of DNA methylation in the pathogenesis of endometriosis and the feasibility of decitabine, a DNA methyltransferase inhibitor, in the treatment of endometriosis. Methods The model of rat endometriosis was established according to autograft in rats. After 4 weeks, the laparotomy was performed twice to determine if the model was successful. The volumes of ectopic foci were measured by vernier calipers and then randomly divided into experimental group (12 Only), PBS group (12) and control group (11). At the same time, normal rats without modeling were selected as blank group (n = 10). The rats in the experimental group were injected intraperitoneally with 5-Aza-2’-deoxycytidine (2.5 mg / kg / d), and the PBS group was injected with the same amount of PBS solution. The control group was given no drug. Immunohistochemical staining and Western Blot were used to detect the expression of DNA methyltransferase 1 in each group. The peritoneal lavage fluid was collected and the content of tumor necrosis factor-α (TNF-α) was detected by Elisa method. Results Thirty-five rats were successfully treated with endometrial autotransplantation. The success rate of modeling was 70% (35/50). The volume of ectopic foci in experimental group was significantly reduced after drug treatment (P <0.05), and the volume of ectopic foci in PBS group and control group had no significant change (P> 0.05). The ectopic endometrial epithelial cells in the experimental group were reduced in volume, gland atrophy and cystic fluid secretion decreased; the expression of DNA methyltransferase 1 in ectopic tumor tissue was lower than that in PBS group and control group (P <0.05) There was no significant difference between the two groups (P> 0.05). After treatment, the content of TNF-α in the peritoneal irrigating fluid of rats in experiment group was lower than that in PBS group and control group. The levels of TNF-α in experimental group, experimental group, PBS group and control group were higher than those in blank group (P <0.05). Conclusion DNA methyltransferase inhibitors can significantly reduce the volume of ectopic foci and promote atrophy of ectopic foci. DNA methyltransferase inhibitors can inhibit DNA methyltransferase expression in ectopic lesions, which may be one of the ways to inhibit the growth of the lesion. DNA methyltransferase inhibitors can inhibit the content of TNF-α in peritoneal cavity of endometriosis rat model.