戊酸雌二醇联合阿司匹林对大鼠宫腔黏连的改善作用

doi:10.13481/j.1671-587x.20190415

摘要/Abstract

摘要： 目的：探讨戊酸雌二醇联合阿司匹林对大鼠宫腔黏连（IUA）的改善作用，阐明两者联用治疗的作用机制。方法：50只健康雌性SD大鼠随机分为对照组、模型组、戊酸雌二醇组、阿司匹林组和戊酸雌二醇联合阿司匹林组（联合组），每组10只，除对照组外其余各组大鼠采用刮宫加感染双重损伤法建立IUA模型，连续给药24 h后取各组大鼠血清和子宫组织，采用ELISA法检测大鼠血清雌二醇水平，HE染色观察大鼠宫腔组织病理形态表现及腺体数量，采用Masson染色观察大鼠子宫内膜纤维化面积比，采用免疫组织化学法检测子宫内膜组织中转化生长因子β1（TGF-β1）、纤溶酶原激活物抑制剂1（PAI-1）和基质金属蛋白酶9（MMP-9）蛋白表达水平。结果：ELISA法检测，与对照组比较，模型组大鼠血清雌二醇水平明显降低（P<0.05）；与模型组比较，戊酸雌二醇组、阿司匹林组和联合组大鼠血清雌二醇水平明显升高（P<0.05）。HE和Masson染色检测，与对照组比较，模型组大鼠宫腔发生黏连、扩大，腔内有积液，宫腔壁细胞排列紊乱，炎性细胞浸润明显，子宫内膜间质纤维化，胶原纤维排列紊乱，子宫内膜腺体数量明显减少（P<0.05），纤维化面积比明显增加（P<0.05）；与模型组比较，戊酸雌二醇组、阿司匹林组和联合组大鼠宫腔黏连、积液、炎性细胞浸润和子宫内膜间质纤维化明显减轻，宫腔壁细胞排列整齐，有少量胶原纤维，子宫内膜腺体数明显增加（P<0.05），纤维化面积比明显降低（P<0.01）；与阿司匹林组比较，联合组大鼠子宫内膜腺体数明显增加（P<0.05），子宫内膜纤维化面积比明显降低（P<0.05）。与模型组比较，戊酸雌二醇组、阿司匹林组和联合组大鼠子宫内膜组织中TGF-β1和PAI-1蛋白表达水平明显降低（P<0.05或P<0.01），MMP-9蛋白表达水平明显升高（P<0.05或P<0.01）；与阿司匹林组比较，联合组大鼠子宫内膜组织中TGF-β1和PAI-1蛋白表达水平明显降低（P<0.05），MMP-9蛋白表达水平明显升高（P<0.05）。结论：戊酸雌二醇与阿司匹林联合应用可降低大鼠子宫内膜组织中TGF-β1和PAI-1表达，上调MMP-9表达，对大鼠IUA具有改善作用。

关键词: 宫腔黏连, 戊酸雌二醇, 阿司匹林, 转化生长因子β1, 纤溶酶原激化物抑制剂1, 基质金属蛋白酶9

Abstract: Objective:To investigate the improvement effect of estradiol valerate combined with aspirin on the intrauterine adhesion (IUA) in the rats, and to elucidate the therapeutic mechanism of estradiol valerate combined with aspirin. Methods:Fifty healthy female SD rats were randomly divided into control group, model group, estradiol valerate group, aspirin group,and estradiol valerate combined with aspirin group (combination group)(n=10);the rats in the other groups except control group were used to establish the IUA models with double injury method of uterine curettage and infection. The serum and uterine tissue were taken from the rats in each group 24 h after continuous administration, the estradiol levels in serum of the rats were observed by ELISA, and the pathological changes and the number of glands in the uterine cavity of the rats in various groups were observed by HE staining, and the ratio of endometrial fibrosis are a was observed by Masson staining. The expression levels of transforming growth factor-β1 (TGF-β1), plasminogen activator inhibitor type-1 (PAI-1) and matrix metalloproteinase-9 (MMP-9) in the endometrium of the rats were detected by immunohistochemistry. Results:The results of ELISA indicated that the estrodiol level in serum of the rats in model group was significantly lower than that in control group(P<0.05);compared with model group,the estrodiol levels in serum of the rats in estradiol valerate group, aspirin group, and combination group were significantly increased (P<0.05). The results of HE and Masson staining showed that compared with control group, uterine cavity adhesion and enlargement, fluid accumulation in the cavity, disorganized arrangement of the cells of uterine cavity wall, significant infiltration of inflammatory cells, endometrial stroma fibrosis,and disordered collagenous fibers were found in model group; the number of endometrial glands in the rats was significantly decreased(P<0.05),and the fibrosis area ratio was significantly increased (P<0.05). Compared with model gorup,the adhesion and effuson in uterine cavity,inflammatory cell infiltration and endometrial stroma fibrosis were alleviated,the cells of uterine cavity wall were arranged neatly,and there was little collagenous fibers in estradiol valerate group,aspirin group,and combination group;the number of endometrial glands was increased(P<0.05),and the fibrosis area ratios were significantlhy decreased(P<0.01).Compared with aspirin group,the number of endometrial glands in combination group was significantly increased(P<0.05),and the fibrosis area ratio was significantly decreased(P<0.05).Compared with model group, the expression levels of TGF-β1 and PAI-1 proteins in the endometrium tissue of the rats in estradiol valerate group, aspirin group, and combination group were significantly decreased (P<0.05 or P<0.01), and the expression levels of MMP-9 protein in the endometrium tissue were significantly increased (P<0.05).The expression levels of TGF-β1 and PAI-1 proteins in the endometrium tissue of the rats in combination group were significantly lower than those in aspirin group (P<0.05), and the expression level of MMP-9 in the endometrium tissue was significantly higher than that in aspirin group (P<0.05). Conclusion:Estradiol valerate combined with aspirin can decrease the expression levels of TGF-β1 and PAI-1 in the endometrium tissue and increase the expression level of NMP-9, which can improve the IUA of the rats.

Key words: intrauterine adhesions, estradiol valerate, aspirin, transforming growth factor-β1, plasminogen activator inhibitor type-1, matrix metalloproteinase-9

中图分类号:

R711.74

刘静乔, 郑燕, 王玉静, 孟亚丽, 徐淑稳, 张华林. 戊酸雌二醇联合阿司匹林对大鼠宫腔黏连的改善作用[J]. 吉林大学学报(医学版), 2019, 45(04): 830-835.

LIU Jingqiao, ZHENG Yan, WANG Yujing, MENG Yali, XU Shuwen, ZHANG Hualin. Improvement effect of estradiol valerate combined with aspirin on intrauterine adhesion in rats[J]. Journal of Jilin University(Medicine Edition), 2019, 45(04): 830-835.

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