表皮生长因子在子宫肌瘤组织中表达和米非司酮的干预作用

Effects of Mifepristone on the expression of EGF in human uterine leiomyoma

目的：探讨米非司酮对子宫肌瘤及子宫肌层组织表皮生长因子（EGF）、雌激素受体（ER）、孕激素受体（PR）的表达和对性激素的影响。方法：11例临床诊断为子宫肌瘤并有手术指征、无肝。肾等内科合并症患者自月经周期第2．3d始口服米非司酮12.5mg／d。连续服用90d，监测服药前后血常规、血清性激素水平、血皮质醇、肝功能的变化，应用B超监测子宫大小、最大子宫肌瘤的变化。停药后立即手术，并选同期手术的临床情况相似的子宫肌瘤患者11例为对照组，用ER、PR单克隆抗体、EGF单克隆抗体免疫组化学法检测子宫肌瘤及子宫平滑肌层组织中的ER、PR、EGF水平。结果：服药后子宫体积平均缩小51．43％，最大肌瘤体积平均缩小28，62％。血红蛋白上升（P=0．017）。服药后血清性激素水平维持在卵泡期水平。对照组子宫肌瘤组织中ER、PR、EGF高于肌层组织（P=0.003，P=0.000，P=0.001），研究组子宫肌瘤组织中的PR高于肌层组织（P=0．040），研究组子宫肌瘤组织中ER、PR、EGF均明显低于对照组（P=0.031，P=0.040，P=0.021），研究组子宫肌层中PR、EGF低于对照组（P=0.041，P=0.003）。结论：子宫肌瘤组织中EGF、ER及PR的表达均高于肌层。使用米非司酮可抑制性激素水平．子宫肌瘤、肌层的EGF表达下降、PR减少，肌瘤中ER减少，孕激素对EGF的上调作用受到抑制从而使肌瘤细胞生长受到抑制至肌瘤缩小。米非司酮用于治疗子宫肌瘤是安全有效的药物。

Objective： To study the effects of Mifepristone on the expression of epidermal growth factor （ EGF）, estrogen receptor （ER） , progesterone receptor （PR） and on sexual hormones in human uterine leiomyoma and myometrium. Methods： 11 patients with u- terine leiomyoma who had surgical indication received 12. 5 mg of Mifepristone daily for 90 days beginning on the second to the third day of menstrual cycle. Complete blood count, serum sexual hormonal parameters, serum cortisol, liver function, ultrasound examination were monitored prior to and at the end of treatment. Hysterectomy or myomectomy was performed when the treatment finished. Leiomyomata and myometrial tissue were obtained for immunohistochemical EGF, ER and PR analyses using monoclonal antibody. Control group included 11 patients who had matched age, weight, size and position of leiomyoma, and operate in the follicular phase of the cycle. Results： After 90 days of Mifepristone treatment, the leiomyoma volume decreased 28. 62% and the uterine volume decreased 51.43%. Hemoglobin was increased （P =0. 017） . Hormonal parameters were within the levels of follicular phase~ In leiomyoma ER, PR, EGF positive rate of control group （P =0. 003, P =0. 000, P =0. 001 ） and PR of study group （P =0. 040） were higher Ihan those in myometrium. In leiomyoma ER, PR, EGF positive rate of study group were significantly less than those of control group in myometrium （P =0.031, P =0.040, P =0.021） . In myometrium PR, EGF positive rate of study group were less than those of control group （P = 0.041, P = 0.003）. Conclusion： In leiomyoma EGF, ER, PR positive rate are higher than those in myometrium. Mifepristone can inhibited leiomyoma growth by inhibiting sexual hormone, resulting in a lower EGF, ER, PR expression in leiomyoma cells and a lower EGF, PR expression in myometrium cell and inhibiting the effect of augmenting EGF by progesterone. Mifepristone is a safe and effective drug for treating uterine leiomyoma.