摘要
目的探讨Wnt/β-catenin信号通路介导间质上皮转化(EMT)在子宫内膜来源间充质干细胞(eMSCs)抑制子宫内膜纤维化中的作用机制。方法将18只雌性SD大鼠随机分为假手术(Sham)组、模型(Model)组和eMSCs组,每组6只。Sham组的大鼠在剖腹手术后不接受任何形式的子宫介入手术。Model组和eMSCs组建立子宫内粘连大鼠模型。eMSCs组在模型损伤后立即移植eMSCs细胞悬液进行治疗,总量为每子宫0.05 ml(2×107细胞/ml)。3周后收集单侧损伤子宫进行苏木精-伊红(HE)染色和Masson染色。通过蛋白质印迹分析子宫内膜纤维化、EMT、Wnt/β-catenin通路蛋白表达。结果Model组大鼠宫腔结构破坏,腺体数量明显减少并积聚大量蓝色胶原纤维,但在eMSCs治疗后子宫内膜腺体数量显著增加,并且纤维化面积显著降低。与Sham组相比,Model组中I型胶原和α-平滑肌肌动蛋白(α-SMA)蛋白的表达水平显著增加(P<0.05),但在eMSCs组中均显著减少(P<0.05)。在Model组中,N-cadherin、Vimentin和ZEB1的表达显著增加,而E-cadherin的表达减少。然而,在eMSCs组中,上述分子蛋白质的变化完全相反。与Sham组相比,Model组β-连环蛋白(β-catenin)和C-myc表达增加(P<0.05)。与Model组相比,eMSCs组中周期蛋白E(CyclinE)、β-catenin和C-myc表达增加(P<0.05)。结论eMSCs可以通过抑制EMT和子宫内膜纤维化来促进子宫内粘连大鼠子宫内膜修复,这种作用部分是通过激活Wnt/β-catenin信号通路来实现。
Objective To explore the mechanism of mesenchymal epithelial transformation(EMT)mediated by Wnt/β-catenin signaling pathway in the inhibition of endometrial fibrosis by endometrial mesenchymal stem cells(eMSCs).Methods Eighteen female SD rats were randomly divided into Sham group,Model group and eMSCs group,with 6 rats in each group.Rats in Sham group merely had laparotomy without any treatment.A rat model of intrauterine adhesion(IUA)was established in the Model group and eMSCs group.In eMSCs group,the total amount of eMSCs cell suspension transplanted immediately after model injury was 0.05 ml(2×107 cells/ml)per uterus for treatment.Three weeks later,the uterus with unilateral injury was collected for hematoxylin-eosin(HE)staining and Masson staining.Endometrial fibrosis,EMT,Wnt/β-catenin pathway protein expression were analyzed by protein blot.Results In the Model group,the structure of the uterine cavity was destroyed and the number of glands were significantly reduced with a large number of blue collagen fibers were accumulated.However,after eMSCs treatment,the number of endometrial glands increased,and the fibrotic area decreased significantly.Compared with Sham group,the expression levels of type I collagen andα-SMA protein in Model group increased significantly(P<0.05),but decreased significantly in eMSCs group(P<0.05).In the Model group,the expressions of N-cadherin,vimentin and ZEB1 increased significantly,while the expression of E-cadherin decreased.However,in eMSCs group,the changes of protein of the above molecules were completely opposite.Compared with Sham group,the expression ofβ-catenin and C-myc increased in Model group(P<0.05).Compared with the Model group,the expressions of CyclinE,β-catenin and C-myc increased in eMSCs group(P<0.05).Conclusion eMSCs can promote endometrial repair in IUA rats by inhibiting EMT and endometrial fibrosis,which is partly achieved by activating Wnt/β-catenin signaling pathway.
作者
靳涛
颜望碧
殷琦
Jin Tao;Yan Wangbi;Yin Qi(Dept of Gynecology,Wuxi Fifth Affiliated Hospital of Jiangnan University,Wuxi 214007;Dept of Gynecology,Wuxi Traditional Chinese Medicine Hospital,Wuxi 214071)
出处
《安徽医科大学学报》
CAS
北大核心
2024年第4期640-646,共7页
Acta Universitatis Medicinalis Anhui
基金
江苏省卫生健康委员会科研项目(编号:20210265)。
