雌、孕激素通过TGF-β影响宫腔粘连的形成

Estrogen and progesterone affect the formation of intrauterine adhesion through TGF-β

目的探讨雌、孕激素对宫腔粘连(intrautine adhesion,IUA)形成的影响及作用机制。方法通过免疫组化和Wes-tern blot检测96例人宫腔粘连组织(IUA组)及30例正常子宫内膜组织(NE组)中雌激素受体(ER)和孕激素受体(PR)的表达。采用Pearson相关检验分析人宫腔粘连组织中转录生长因子-β(TGF-β)和ER、PR表达的相关性。将24只雌兔分成4组:低雌低孕组(切除两侧卵巢)、低雌高孕组(切除两侧卵巢+1.0 mg黄体酮)、高雌低孕组(切除两侧卵巢+1.0 mg苯甲酸雌二醇)和正常生理组(切除两侧卵巢周边脂肪组织),每组6只。通过HE及Masson染色评估子宫内膜纤维化状况。将子宫内膜癌细胞RL95-2分为4组:对照组、低雌低孕组(E_(2)2 nmol/L+P 2 nmol/L)、低雌高孕组(E_(2)2 nmol/L+P 15 nmol/L)和高雌低孕组(E_(2)15 nmol/L+P 2 nmol/L),Western blot检测TGF-β表达。结果ER在IUA组织中的阳性表达率及相对表达量均显著低于正常子宫内膜组织(18.8%vs 40.0%,P<0.01;0.28±0.04 vs 0.68±0.03,P<0.05),而PR在IUA组织中的阳性表达率及相对表达量均显著高于正常子宫内膜组织(34.4%vs 20.0%,P<0.01;1.47±0.06 vs 0.51±0.04,P<0.05)。在宫腔粘连组织中,TGF-β与ER的表达呈负相关(r=-0.88,P<0.01),TGF-β与PR的表达呈正相关(r=0.81,P<0.05)。与正常生理组相比,低雌高孕组子宫内膜纤维化评分显著升高(P<0.01),高雌低孕组则显著降低(P<0.01),而低雌低孕组无明显变化(P>0.05)。低雌高孕组RL95-2细胞中TGF-β的表达显著高于对照组(P<0.01),高雌低孕组显著低于对照组(P<0.01)。结论雌、孕激素影响IUA的形成,其机制可能与TGF-β的表达有关。

Objective To explore the influence and mechanism of estrogen and progesterone on the formation of intrautine adhesion(IUA).Methods Immunohistochemistry and Western blot were used to detect the expression of estrogen receptor(ER)and progesterone receptor(PR)in 96 cases of intrautine adhesion(IUA group)and 30 cases of normal endometrial tissues(NE group).The correlation between TGF-βand ER,PR expression in human IUA tissues were analyzed using Pearson correlation test.A total of 24 female rabbits were divided into 4 groups:low estrogen and low progesteron group(resection of bilateral ovaries),low estrogen and high progesteron group(resection of bilateral ovaries+1.0 mg progesterone),high estrogen and low progesterone group(resection of bilateral ovaries+1.0 mg estradiol benzoate)and normal physiological group(resection of peripheral adipose tissue of bilateral ovaries),with 6 rabbits in each group.The endometrial fibrosis status was observed by HE staining and Masson staining.Endometrial cancer cells RL95-2 were divided into four groups:control group,low-estrogen and low progesterone group(E_(2)2 nmol/L+P 2 nmol/L),low-estrogen and high progesterone group(E_(2)2 nmol/L+P 15 nmol/L),and high-estrogen and low progesterone group group(E_(2)15 nmol/L+P 2 nmol/L).The expression of TGF-βwas detected by Western blot.Results The positive expression rate and the relative expression level of ER in IUA tissues were significantly lower than those in normal endometrium tissues(18.8%vs 40.0%,P<0.01;0.28±0.04 vs 0.68±0.03,P<0.05),and the positive expression rate and the relative expression level of PR in IUA tissues were significantly higher than those in normal endometrium tissues(34.4%vs 20.0%,P<0.01;1.47±0.06 vs 0.51±0.04,P<0.05).In IUA tissues,TGF-βwas negatively correlated with ER expression(r=-0.88,P<0.01),and positively correlated with PR expression(r=0.81,P<0.05).Compared with normal physiological group,the endometrial fibrosis scores were significantly increased in low estrogen and high pregesterone group(P<0.01),significantly decreased in high estrogen and low pregesterone group(P<0.01),and showed no significant change in low estrogen and low pregesterone group(P>0.05).Compared with control group,TGF-βexpression in RL95-2 cells was significantly increased in low estrogen and high pregesterone group(P<0.01),while TGF-βexpression was significantly decreased in high estrogen and low pregesterone group(P<0.01).Conclusion Estrogen and progesterone affect the formation of IUA,and the mechanism may be related to the expression of TGF-β.