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LNG-IUS治疗子宫肌瘤的临床效果及机制探讨 被引量:11

Observation of clinical effects of intrauterine progesterone treating uterine leiomyoma and the study of the related mechanisms
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摘要 目的:观察应用左炔诺孕酮宫内缓释系统(LNG-IUS)治疗子宫肌瘤的临床效果,探讨性激素对子宫肌瘤细胞的增殖调节作用及左炔诺孕酮(LNG)对肌瘤细胞凋亡的影响。方法:(1)选择36例确诊为子宫肌瘤的患者,于月经后3~5d刮除大部分子宫内膜后放置LNG-IUS。置器后第1,3,12,48个月随访,观察月经量改变、血红蛋白水平的变化、B超测量子宫肌瘤瘤体积变化、子宫容积及置器后不良反应的发生率。(2)四甲基偶氮唑盐(MTT)法检测LNG或17-β雌二醇(E_2)对原代培养人子宫肌瘤细胞(UtLMC)的增殖调节作用;流式细胞术测定LNG对细胞凋亡率的影响。结果:(1)研究对象在置器1个月后月经量减少,血红蛋白水平明显提高,子宫容积较放置前缩小;随置器时间延长临床效果改变更为明显(P=0.028);但子宫肌瘤体积无明显变化;月经减少和闭经的发生率随放置时间的延长逐渐增加。(2)10.0μg/ml LNG开始抑制肌瘤细胞的生长,随浓度增加及时间延长抑制作用加强。低浓度E_2(≤3660pmol/L)抑制子宫肌瘤细胞的增殖能力,但高浓度E_2(≥36 600pmol/L)促进子宫肌瘤细胞的增殖。流式细胞术分析,与对照组相比,LNG组细胞凋亡率随LNG浓度的增加而逐渐升高,具有浓度依赖性(r^2=0.9799);10.0μg/ml LNG作用72h后,肌瘤细胞早期凋亡出现明显(P=0.036)。结论:宫腔放置LNG-IUS能有效减少患者月经量,改善贫血症状,全身副作用较小,且能使子宫容积缩小。其作用机制可能是性激素尤其是一定浓度的孕激素抑制子宫肌瘤细胞增殖,并诱导其凋亡。 Objective:To observe the clinical effects of levonorgestrel-intrauterine releasing system(LNG-IUS)treating uterine fibroid patients,and to explore the influence of levonorgestrel on uterine leiomyoma cells(UtLMCs)prolifera-tion and apoptosis.Methods:(1)LNG-IUS were inserted in thirty-six patients with uterine fibroid who were scraped off most endometrium 3-5 days after menstruation.In the 1-,3-,12-,48-month followed up,the menstrual blood vol-ume,hemoglobin level,uterine volume,expulsion rate and adverse event rate were observed,and myoma volume measured by B ultrasound.(2)After LNG and E2 treatment,the growth rate of cultured primary uterine leiomyoma cell was detected by methyl thiazolyl tetrazolium(MTT)assay.Cell apoptosis rate was determined by morphological changes and flow cytometry.Results:(1)Menstrual blood volume was reduced significantly,the hemoglobin level significant rose,and the uterine volume decreased in the first month after the LNG-IUS inserted.These clinical changes were more and more significant over time,which had significant different compared to patients inserted LNG-IUS be-fore(P=0.028).However,there was no significant change in the volume of uterine fibroids.The rate of menstruation volume had reduced and amenorrhea had increased gradually with the time extension of LNG-IUS inserted.(2)After 10μg/mL LNG treatment,the proliferation rate of uterine leiomyoma cells was suppressed.Low concentration of E2(≤1 ng/mL)inhibited the proliferation of uterine leiomyoma cells,but high concentration of E2(≥10 ng/mL)signifi-cantly promoted uterine leiomyoma cell proliferation.Flow cytometry analysis showed that compared with the control group,after LNG treatment,the apoptosis rate of the cell increased in a concentration dependent manner,with the correlation coefficient of r2 =0.9799.After LNG(10 μg/mL)treatment 72h,the early leiomyoma cell apoptosis significant changed(P〈0.05).Conclusion:LNG-IUS can effectively reduce the patient's menstrual volume,improve symptoms of anemia,and reduce uterine volume with few systemic side effects.The mechanism might be that LNG can suppress the proliferation and induce apoptosis of the uterine leiomyoma cells.
作者 徐青 付子毅 马慧媛 陈艳 吴晓丽 徐娟 XU Qing;FU ZiYi;MA Huiyuan;CHEN Yah;WU Xiaoli(Maternity Hospital Affiliated to Nanjing Medical University, Jiangsu, 210004)
出处 《中国计划生育学杂志》 2018年第4期274-278,共5页 Chinese Journal of Family Planning
基金 国家自然科学基金(81202042) 南京市医学科技发展基金(QRX11212) 南京医科大学科技发展基金(2015NJMUZD063)
关键词 左炔诺孕酮宫内缓释系统 子宫肌瘤 临床效果 机制研究 levonorgestrel-intrauterine releasing system Uterine fibroids Clinical effects Mechanism research
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