长期放置宫内避孕器对子宫微环境的影响及其机理的研究

目的　研究长期放置宫内避孕器 (IUD)后子宫局部微环境的变化及其分子机理。方法　对 6 2例使用IUD和 2 7例未使用IUD(对照组 )妇女 ,利用放射免疫法检测宫腔冲洗液中细胞因子和抗体水平 ;用免疫组化技术测定子宫内膜T淋巴细胞亚群 ;用电镜观察子宫内膜的超微结构 ;采用银染PCR 单链构型多态性分析 (SSCP)技术检测子宫内膜 p16、p5 3及K ras基因突变。 结果　与对照组相比 ,惰性及含铜IUD组的宫腔冲洗液中肿瘤坏死因子 (TNF) α浓度无明显变化 (P >0 0 5 ) ,但含铜IUD组的白细胞介素 (IL) 2浓度为 0 39μg/L± 0 18μg/L、分泌型IgA浓度为 2 0 0 0 μg/L± 12 2 4 μg/L ,对照组为 0 96 μg/L± 0 15 μg/L及 3377μg/L± 190 6 μg/L (P <0 0 5 ) ;含铜IUD组与对照组相比子宫内膜CD8+ 、CD4 + 淋巴细胞的分布差异有显著意义 (P <0 0 5 ) ;长期放置两种IUD后子宫内膜的超微结构观察均未见坏死及异型改变 ;P16、p5 3、K ras基因在各组中均无突变。 结论　长期放置惰性IUD和含铜IUD是安全而有效的 ,但含铜IUD对宫腔局部的免疫功能有一定的影响。

Effects of long-term installation of intrauterine devices on intrauterine microenvironment

OBJECTIVES: To study the effect of long-term installation of intrauterine devices (IUD) on the intrauterine microenvironment. METHODS: Eighty-nine healthy 26 - 50-year-old women undergoing physical examination or having their IUD removed were recruited. Among them 62 had used IUDs, including 32 inert IUD (I-IUD) and 30 copper releasing IUD (T-IUD), for 5 - 20 years, and 27 women without installation of IUD were used as controls. In the 3rd to 13th day of menstrual cycle, 3 ml of irrigation of intrauterine cavity were collected to examine the concentrations of tumor necrosis factor-alpha (TNF-alpha), interleukin 2 (IL-2) and secretary IgA (SIgA) by radioimmunoassay (RIA). Hysteroscopy was used to obtain 3 pieces of endometrium at the place where the IUD was attached for each subject. Three pieces of endometrium were curretted from each control during the proliferative stage. Thirty specimens of endometrium, including 10 cases with I-IUD, 10 cases with T-IUD, and 10 control cases were used to examine the distribution of T cell subset by immunohistochemistry. Fifteen specimens of endometrium, including 6 cases with I-IUD, 6 cases with T-IUD, and 3 control cases, were used to examine the endometrial ultrastructure by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Twenty-five specimens of endometrium, including 10 cases with I-IUD, 10 cases with T-IUD, and 5 control cases, were used to detect the expression and mutation of P16, P53 and K-ras by PCR-SSCP technique. RESULTS: There was no significant difference in TNF-alpha level in the irrigation among the three groups (P > 0.05). IL-2 and SIgA levels (0.39 +/- 0.18) microg/L and (2000 +/- 1224) microg/L respectively) in the T-IUD group were significantly lower than those in the control group (0.96 +/- 0.15) microg/L and (3377 +/- 1906) microg/L respectively, both (P < 0.05). There was a significant difference in the population of T lymphocytes (CD(8)(+) and CD(4)(+) lymphocytes) between the T-IUD group and control group (P < 0.05). SEM and TEM showed no necrosis and atypia in the endometrial cells of I-IUD group and T-IUD group. There was no positive expression of gene p16, p53 and K-ras in the endometrium of the three groups. CONCLUSION: It is safe and effective using I-IUD or T-IUD for a long time, however, T-IUD has some effects on intrauterine local immune function.