不同剂量戊酸雌二醇防治大鼠宫腔粘连的作用研究

Effects of different doses of estradiol valerate on intrauterine adhesion in rats

目的:研究不同剂量的戊酸雌二醇(estradiol valerate,E2V)对大鼠宫腔粘连(intrauterine adhesions,IUA)的防治效果。方法:将48只8~10周龄健康雌性SD大鼠随机分为8组:空白对照组、实验对照组、3个雌激素预防组(低、中、高剂量)、3个雌激素治疗组(低、中、高剂量)。收集各组大鼠子宫组织,HE染色观察子宫内膜腺体,MASSON染色观察子宫内膜纤维化程度,免疫组化法检测子宫内膜转化生长因子-β1(transforming growth factor-β1,TGF-β1)、基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)、雌激素受体-α(estrogen receptor-α,ER-α)的表达水平。结果:与实验对照组相比,3个雌激素预防组大鼠的子宫内膜腺体计数增多(P值均为0.000)、纤维化面积降低(P_(低雌A组)=0.013,P_(中雌A组)=0.021,P_(高雌A组)=0.003),差异均有统计学意义,3个雌激素治疗组大鼠的子宫内膜腺体计数(P_(低雌B组)=0.536,P_(中雌B组)=0.536,P_(高雌B组)=1.000)及纤维化面积(P值均为1.000)与实验对照组相比均无显著性差异;6个雌激素组的子宫内膜TGF-β1表达水平均降低(P值均为0.000),其中中、高剂量组均低于低剂量组(P值分别为0.003及0.002),而中、高剂量2组相比无差异(P=0.842);6个雌激素组子宫内膜MMP-9表达水平均升高(P值均为0.000),中、高剂量组均高于低剂量组(P值均为0.000),而中、高剂量2组相比无差异(P=0.379);6个雌激素组子宫内膜ER-α表达水平均有升高(P值均为0.000),中、高剂量组均高于低剂量组(P值均为0.000),而中、高剂量2组相比无差异(P=0.513)。结论:在大鼠IUA建模早期应用雌激素,可显示较好疗效,但ER-α饱和后,其疗效不随剂量增加而增强;在建模完成后应用雌激素,治疗效果欠佳,考虑是否与单一治疗有关,如能增加其他治疗方法也许能增强疗效。

Objective:To evaluate the prevention and treatment effect of estrodiol valerate on rats intrauterine adhesion. Methods:Forty-eight 8-10 weeks old female SD rats were randomized into 8 groups,6 rats per group:blank control group,experimental control group,three prevention estrogen groups(low dose,medium dose,high dose),three treatment estrogen groups(low dose,medium dose,high dose). The uteri were collected. Number of endometrial glands was tested by HE staining;degree of endometrial fobrosis was evaluated by Masson staining,and the endometrial expressions of transforming growth factor-β1(TGF-β1),matrix metalloproteinase-9(MMP-9)and estrogen receptor-α(ER-α)were detected by immunohistochemistry. Results:In three prevention estrogen groups,endometrial glands increased(the P values were all 0.000),endometrial fibrosis area ratio decreased(the P values were:P_(low group A)=0.013,P_(medium group A)=0.021,P_(high group A)=0.003 respectively),with statistically significant differences. In three treatment estrogen groups,endometrial glands(P values were:P_(low group B)=0.536,P_(medium group B)=0.536,P_(high group B)=1.000)and endometrial fibrosis area ratio(the P values were all 1.000)had no improvement compared with those of experimental control group. TGF-β1 expression level was much lower in 6 estrogen groups than in experimental control group(the P values were all 0. 000);lower in medium dose and high dose estrogen group than in of low dose estrogen group(the P values were 0.003 and 0.002 respectively);there was no significant difference between high dose group and medium dose group(P=0.842). MMP-9 expression level was much higher in 6 estrogen groups than in experimental control group(the P values were 0. 000),higher in medium dose and high dose estrogen group than in low dose group(P=0.000,P=0.379). ER-α expression level was much higher in 6 estrogen groups than in experimental control group(the P values were all 0.000),higher in medium dose and high dose estrogen group than in low dose group(the P values were 0. 000),there was no significant difference between high dose group and medium dose group(P=0.513). Conclusion:Estrodiol valerate can prevent rat intrauterine adhesion. The prevention effect is not en hanced with the increase of the dose after the saturation of ER-α. Separate application of E2 V to treat IUA is helpless,comprehensive treatment like TCRA is needed.