目的 研究染料木素对子宫内膜异位症(EM)裸鼠模型体内病灶组织生长及黏着斑激酶(FAK)活性的影响,探讨其作为EM治疗药物的可能性及其作用机制.方法 建立EM裸鼠模型,随机分为染料木素低(0.5 mg/kg)、中(1.5 mg/kg)、高(4.5 mg/k g)三个剂量组、雌激素受体拮抗剂他莫昔芬(4.5 m/kg)对照组、溶剂对照组和空白对照组,每组5只;隔日注射1次,连续给药2周;每周测量1次病灶直径.并采用化学发光分析法测量各组裸鼠体内雌激素含量,采用免疫印迹法比较各组病灶组织FAK及其下游信号蛋白AKT的表达及其磷酸化水平变化情况.结果 和空白对照和溶剂对照相比,染料木素各剂量组均能显著抑制EM裸鼠模型体内病灶的生长(P＜0.05),并呈现剂量依赖性的作用特点,其中大剂量组与他莫昔芬对照组相比差异也有统计学意义(P＜0.05).分析其作用机制,发现染料木素对EM模型体内雌激素水平没有影响,但能够下调FAK及其下游AKT蛋白的磷酸化水平,而对照药他莫昔芬无此作用.结论 染料木素可以有效阻抑EM病灶组织生长,抑制FAK及其下游AKT蛋白活化可能是其作用机制之一.%Objective To investigate the effect of genistein on the growth and focal adhesion kinase (FAK) activity of human endometrium in nude mice endometriosis model, and explore the potential mechanism of genistein action. Methods Endometriosis nude mice models were established and randomly divided into six groups: low-dose genistein (0.5 mg/kg) group,middle-dose genistein (1.5 mg/kg) group,high-dose genistein (4.5 mg/kg) group, estrogen receptor antagonist tamoxifen (4. 5 mg/kg) group, normal saline control group and DMSO solvent control group. The growth in human endometrium transplanted into nude mice was measured once each week. The estrogen content in nude mice model was determined by chemiluminescence immunoassay method, and FAK and AKT proteins and their phosphorylated forms in the endometrium tissues were detected" by western blot. Results Compared with normal saline or DMSO control group, genistein could have dose-dependent inhibitory effects on the growth of human endometrium in nude mice endometriosis model (P<0.05) ,and there was a significant difference between tamoxifen group and high-dose genistein group (P <0. 05) ;Genistein did not influence estrogen content,but could downregulate the phosphorylation levels of FAK and AKT in human endometrium. Conclusion Genistein could effectively inhibit the endometrial growth in nude mice endometriosis model. The inhibition on FAK and AKT phosphorylation may be a part of the mechanism of genistein.
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