戊酸雌二醇对大鼠宫腔粘连形成的预防作用观察

Preventive effect of estradiol valerate on intrauterine adhesion formation in rats

目的探讨雌二醇对大鼠宫腔粘连形成的预防作用及其机制。方法 30只雌性SD大鼠随机均分为5组,采用刮宫加感染双重损伤法制作大鼠宫腔粘连模型,实验处理因素为戊酸雌二醇灌胃。空白对照组(A)大鼠不予造模也不施加雌二醇处理;生理量雌激素组(B)造模但不给予雌二醇;低剂量雌激素组(C)、中剂量雌激素组(D)、高剂量雌激素组(E)于造模后分别给予剂量为0.206、0.514、1.028mg/(kg·d)的戊酸雌二醇灌胃。采用ELISA法测定各组大鼠戊酸雌二醇灌胃前后的血清雌二醇浓度,采用HE染色观察各组大鼠子宫内膜腺体数量,Masson染色计算子宫内膜纤维化面积,并通过免疫组化法检测子宫内膜组织中转化生长因子β(TGF-β)、基质金属蛋白酶9(MMP-9)的表达情况。结果戊酸雌二醇灌胃后,C、D、E组血清雌二醇水平较A、B组明显增高(P<0.05);随着灌胃戊酸雌二醇量增加,血清雌二醇水平也升高,差异有统计学意义(P<0.05)。与B组相比,C、D、E组子宫内膜腺体数目明显增多,纤维化面积比降低(P<0.05),但D、E组间比较差异无统计学意义。与B组比较,C、D、E组子宫内膜TGF-β表达明显降低(P<0.05),MMP-9表达明显升高(P<0.05),但D、E组间差异无统计学意义。结论雌二醇可减轻子宫内膜损伤后宫腔粘连的形成,在一定范围内随着雌二醇量的增加改善作用会更加明显。

Objective To investigate the preventive effect and the mechanism of estradiol on the formation of intrauterine adhesion in rats. Methods Thirty female SD rats were randomly assigned into 5 groups（6 each）, and rats intrauterine adhesion model was reproduced by curettage and infection. Estradiol valerate was gavaged for prevention of adhesion. Rats in control group（A） were not given intrauterine injury or estradiol. In physiological estrogen group（B） intrauterine injury was reproduced, but no estradiol valerate was given. The rats in low dose estrogen group（C）, moderate dose estrogen group（D） and high dose estrogen group（E） were treated with estradiol valerate of 0.206, 0.514 or 1.028mg/（kg·d） respectively after reproduction of the model. ELISA was used to determine the serum concentrations of estradiol. HE staining was performed to observe the number of endometrial glands in rats. Masson staining was used to calculate the area of endometrial fibrosis, and immunohistochemical method was employed to detect the expressions of matrix metalloproteinase 9（MMP-9） and transforming growth factor beta（TGF-β）. Results On account of administration of estradiol valerate, the serum estradiol levels were significantly higher in group C, D and E than in group A and B, and the serum estradiol levels increased along with the increase of dosage of estradiol（P〈0.05）. Compared with group B, rats in group C, D and E presented increased number of endometrial glands and decreased ratio of endometrial fibrosis area（P〈0.05）, but no significant difference was found between group D and group E. Compare to group B, rats in Group C, D and E showed higher MMP-9 levels and lower TGF-β levels（P〈0.05）, but no significant difference was found between group D and group E. Conclusion Estradiol may reduce the formation of intrauterine adhesion, and the effect is positively correlated with the dosage of estradiol used.