不同水平雌激素在宫腔粘连形成中的作用及相关机制

摘要

Objective To investigate the effect and mechanism of the formation of intrauterine adhesion (IUA) at different dose of estrogen. Methods Thirty-three New Zealand female rabbits were randomly divided into low estrogen group, normal physiological estrogen group, moderate estrogen group and high estrogen group. Animals of the low, moderate and high groups were ovariectomized (OVX) while normal group underwent sham operation. The moderate and high group animals received 0. 5 mg or 1.0 mg estradiol benzoate after OVX twice a week respectively. Two weeks later, all animals received curettage under direct vision. Serum was collected regularly to determine levels of estradiol (E2), transforming growth factor β1 (TGF-β1) and basic fibroblast growth factor (bFGF). Two weeks after curettage, we cut open cavity to collected endometrium for HE and Masson staining to score extent of endometrial fibrosis and IUA.Results The score of extent of endometrial fibrosis in high group (6. 1 ± 1.5) was higher than those in low estrogen group, normal estrogen group, moderate estrogen group (2. 7 ± 2. 1, 1.2 ± 1.8, 2. 7 ± 2. 0; all P <0. 05). The score of extent of IUA in high group (4. 0 ±2. 5) was higher than that in any other groups (0. 3 ± 0. 8, 1.0 ± 1.6, 1.7 ± 1.9; all P < 0. 05). The levels of TGF-β1 and bFGF was correlated with the level of E2 positively (P < 0. 01) and they had positive relationship with extent of endometrial fibrosis and IUA (P <0. 05). Conclusion High estrogen could accelerate endometrial fibrosis and IUA by promoting expression of TGF-β1, bFGF.%目的 探讨不同水平雌激素在宫腔粘连形成中的作用及相关机制.方法 33只雌兔随机分为低雌激素组(8只)、生理量雌激素组(8只)、中量雌激素组(8只)和高雌激素组(9只).低雌激素组切除双侧卵巢;生理量雌激素组切除双侧卵巢周围的脂肪等组织;中量雌激素组及高雌激素组切除双侧卵巢后分别给予0.5、1.0 mg苯甲酸雌二醇每周两次肌内注射.基础状态下及用药两周测定血清雌二醇、转化生长因子β1(TGF-β1)、碱性成纤维细胞生长因子(bFGF)水平,并行直视下官腔搔刮.继续用药,在搔刮后两周剖探宫腔,多点获取子宫内膜行HE及Masson染色,对内膜纤维化及宫腔粘连程度行半定量评分.结果 高雌激素组兔的子宫内膜纤维化程度评分[(6.1±1.5)分]高于低雌激素组、生理量雌激素组及中量雌激素组[评分分别为(2.7±2.1)、(1.2±1.8)、(2.7±2.0)分],分别比较,差异均有统计学意义(P<0.01).高雌激素组兔的宫腔粘连程度评分[(4.0±2.5)分]高于另外3组[分别为(0.3±0.8)、(1.0±1.6)、(1.7±1.9)分],分别比较,差异均有统计学意义(P<0.05).各组血清TGF-β1、bFGF水平与雌二醇水平均呈直线正相关(P均<0.01),并且均与子宫内膜纤维化及宫腔粘连程度呈正相关(P均<0.05).结论 高雌激素环境能升高血清TGF-β1、bFGF水平,从而促进子宫内膜纤维化的发生、加剧官腔粘连形成.