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子宫内膜间充质干细胞对小鼠模型薄型子宫内膜的修复作用 被引量:7

Repairing effect of uterus-derived mesenchymal stem cells on thin endometrium in mouse model
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摘要 目的观察小鼠子宫内膜间充质干细胞对小鼠模型薄型子宫内膜的修复作用。方法选择8周龄动情期规律C57BL/6J小鼠共288只,随机分为空白对照组、模型对照组、干细胞移植组,每组96只。空白对照组不做任何处理;模型对照组宫腔注射95%乙醇损伤后立即原位注射PBS 0.1 ml,3 d后尾静脉注射PBS 1 ml;干细胞移植组宫腔注射95%乙醇损伤后立即原位注射子宫内膜间充质干细胞0.1 ml,3 d后尾静脉注射子宫内膜间充质干细胞1 ml,干细胞浓度为5×105/ml。每组根据取样时间(3 d、7 d、14 d、30 d)不同分为4小组,取样当日,半数小鼠子宫组织取样,4%多聚甲醛固定送检,进行子宫内膜厚度、HE染色、免疫组化等检测;另半数小鼠与确定有生殖能力C57BL/6J雄鼠合笼,进行生育力评估。结果干细胞移植组小鼠子宫内膜厚度在各时间点均显著厚于模型对照组(P<0.05),但与空白对照组仍有一定距离(P<0.05)。HE染色结果显示,干细胞移植后的受损子宫内膜上皮层及基质层均增厚,腺体增加。免疫组化结果显示,干细胞移植组角蛋白、波形蛋白、VEGF、ERα各项指标均有显著上升,与模型对照组有显著性差异(P<0.05)。生育力评估发现,模型对照组生育率接近于0(仅30 d亚组1例),而干细胞移植组生育率显著升高,30 d亚组生育率达50%,接近空白对照组(66.7%)。结论小鼠子宫内膜间充质干细胞对薄型子宫内膜有显著改善。 Objective:To observe the repair effect of endometrial mesenchymal stem cells(MSCs)on the thin endometrium of mice model.Methods:A total of 288 C57BL/6J mice with regular estrous stage aged 8 weeks were selected and randomly divided into blank control group,model control group and stem cell transplantation group,with 96 mice in each group.No any treatment was done in blank control group.The mice in model control group were injected with 0.1 ml PBS in situ immediately after uterine cavity infusion of 95%ethanol,and 1 ml PBS was injected into the tail vein 3 days later.The mice in the stem cell transplantation group were injected with 0.1 ml MSCs in situ immediately after uterine cavity infusion of 95%ethanol,and 1 ml MSCs were injected into tail vein at a concentration of 5×105/ml three days later.The mice in each group were divided into four subgroups according to the sampling time(3,7,14 and 30 days).On the sampling day,the uterine tissues of half the mice were collected and fixed with 4%paraformaldehyde for detection of endometrial thickness,HE staining and immunohistochemistry.Another half mice were mated with fertile C57BL/6J males for fertility evaluation.Results:The endometrium of the stem cell transplantation group was significantly thicker than the model control group at all the time points,(P<0.05),but there was still a certain distance from the blank control group(P<0.05).HE staining results showed that the damaged endometrial cortex and stromal layer were thickened and glands were increased after stem cell transplantation.Immunohistochemical results showed that the indexes of cytokeratin,vimentin,VEGF and ER α were significantly increased in the stem cell transplantation group,which were significantly different from those in the model control(P<0.05).Fertility evaluation showed that the fertility rate in the model control group was close to 0(only 1 pregnancy in the 30-day subgroup),while the fertility rate of the stem cell transplantation group was significantly increased,while the fertility rate reached 50%in the 30-day subgroup,close to the blank control group(66.7%).Conclusions:Mouse endometrial mesenchymal stem cells can significantly improve the thin endometrium.
作者 李瑞娇 张汝月 郭兴萍 张引红 李红霞 LI Rui-jiao;ZHANG Ru-yue;GUO Xing-ping;ZHANG Yin-hong;LI Hong-xia(Reproductive Science Institute of Shanxi Province,Shanxi Key Laboratory of Birth Defect&Cell Regeneration,Taiyuan 030006)
出处 《生殖医学杂志》 CAS 2021年第1期68-75,共8页 Journal of Reproductive Medicine
基金 山西省重点研发计划资助项目(201603D321110)。
关键词 薄型子宫内膜 子宫内膜间充质干细胞 干细胞移植 Thin endometrium Endometrial mesenchymal stem cells Stem cell transplantation
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