宫腔粘连大鼠模型的构建以及二甲双胍对模型大鼠生育能力的改善作用  

Establishment of intrauterine adhesion rat model and improvement effect of metformin on fertility of rat model

作　　者：江梅 姜经航 邵帅 王洋 丁涛 JIANG Mei;JIANG Jing-hang;SHAO Shuai;WANG Yang;DING Tao(Reproductive Medicine Center,Jingmen No.2 People′s Hospital,Jingmen 448000,China)

机构地区：[1]湖北省荆门市第二人民医院生殖医学中心,荆门市448000

出　　处：《广西医学》2021年第1期62-66,共5页Guangxi Medical Journal

基　　金：湖北省自然科学基金(2018CFC859);湖北省荆门市科学技术研究与开发计划(2019YFZD044)。

摘　　要：目的构建大鼠宫腔粘连模型,并探讨二甲双胍对宫腔粘连大鼠生育能力的改善作用。方法(1)取30只SD雌性大鼠随机分为对照组和造模组各15只,其中造模组采用刮宫联合感染法构建宫腔粘连大鼠模型。于造模后第7天、第14天以及第21天,取各组大鼠子宫组织,检测子宫内膜腺体数量、子宫内膜厚度、子宫内膜纤维化比例,以及转化生长因子β1(TGF-β1)、Smad 3、纤维粘连蛋白(FN)、α-平滑肌肌动蛋白(α-SMA)的蛋白及其mRNA的表达水平。(2)另取15只SD雌性大鼠随机分为对照组、造模组、造模+二甲双胍组各5只,后两组采用同法构建宫腔粘连大鼠模型。造模14 d后,造模+二甲双胍组开始给予二甲双胍灌胃,其他两组给予生理盐水灌胃。服药4周后,将雌性大鼠与雄性大鼠合笼,评估大鼠孕囊数。结果(1)随着造模时间的延长,造模组大鼠的子宫内膜腺体数量减少、子宫内膜厚度变薄、宫内膜内膜纤维化比例增加,且以上表现均较对照组更严重(均P<0.05);TGF-β1、Smad 3蛋白及mRNA的表达水平,以及FN和α-SMA的mRNA表达水平均增高,且高于对照组(均P<0.05)。(2)对照组、造模+二甲双胍组、造模组大鼠的子宫内孕囊数依次降低(均P<0.05)。结论刮宫联合感染法能够构建稳定的宫腔粘连大鼠模型,且模型的子宫组织纤维化相关指标出现高表达。二甲双胍能够改善宫腔粘连大鼠的生育能力。Objective To establish a rat model of intrauterine adhesion(IUA),and to explore the improvement effect of metformin on fertility of IUA rats.Methods(1)Thirty SD female rats were randomized to control group(n=15)or model group(n=15),among them,the model group used the method of curettage combined with infection to establish a rat model of IUA.On the 7th,14th and 21st day after modeling,the uterine tissues of all rats were removed to detect the number of endometrial glands,endometrial thickness,proportion of endometrium with fibrosis,as well as the protein and mRNA expression levels of transforming growth factorβ1(TGF-β1),Smad 3,fibronectin(FN)andα-smooth muscle actin(α-SMA).(2)Another 15 SD female rats were randomized to control group(n=5),model group(n=5)or model+metformin group(n=5),and the modeling for IUA was conducted in the latter two groups using the same approach.After 14 days of modeling,the model+metformin group was treated with metformin by intragastric gavage,and the other two groups with normal saline by intragastric gavage.After four weeks of administration,the female rats were mated with male rats,then the number of gestational sac was assessed in all rats.Results(1)Rats in the model group exhibited fewer endometrial glands,thinner endometrium,increased proportion of endometrium with fibrosis with the increase of modeling time,and those aforementioned manifestations were severer as compared with the controls(all P<0.05);the protein and mRNA expression levels of TGF-β1 and Smad 3,as well as the mRNA expression levels of FN andα-SMA were increased in the model group,which were higher than the controls(all P<0.05).(2)The number of intrauterine gestational sac declined in the control group,the model+metformin group and the model group successively(all P<0.05).Conclusion The stable rat model of IUA is established by the method of curettage combined with infection;in addition,the indicators related to uterine fibrosis are highly expressed in the model.Metformin can improve the fertility of IUA rats.

关 键 词：宫腔粘连 刮宫 感染法 大鼠模型 二甲双胍 转化生长因子β1 Smad 3 纤维粘连蛋白 Α-平滑肌肌动蛋白 

分 类 号：R711.32[医药卫生—妇产科学]