人羊膜上皮细胞移植对大鼠子宫瘢痕模型子宫内膜的改善及对MMP-8、VEGF的影响
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新乡医学院三全学院

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Effects of human amniotic epithelial cells transplantation on the improvement of endometrium and MMP-8, VEGF in rat model of uterine scar
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新乡医学院三全学院

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    摘要:

    目的:探讨人羊膜上皮细胞(hAECs)移植对大鼠子宫瘢痕模型子宫内膜的改善及对基质金属蛋白酶8(MMP-8)、血管内皮生长因子(VEGF)的影响。方法:建立大鼠子宫瘢痕模型,并随机分为模型组及移植组,每组各18只,另取18只大鼠作为假手术组。移植组大鼠于子宫瘢痕处注射hAECs,模型组及假手术组仅给予等量PBS。4周后,取各组8只大鼠子宫组织,HE染色观察组织形态学变化,测量子宫内膜厚度和腺体数量;Masson染色观察子宫内膜纤维化情况;细胞角蛋白和整合素β3免疫组化染色分别评估子宫内膜生长和容受性;RT-qPCR技术检测子宫内膜组织中MMP-8、VEGFA mRNA表达水平;Western blotting法检测组织中MMP-8、VEGFA蛋白表达水平;8周后,取各组剩余10只大鼠进行妊娠能力测定。结果:与假手术组比较,模型组及移植组大鼠子宫内膜厚度、腺体数、角蛋白和整合素β3 IOD值、MMP-8、VEGFA mRNA和蛋白相对表达水平、妊娠率和子宫胚胎数降低(P<0.05);与模型组比较,移植组大鼠子宫内膜厚度、腺体数、角蛋白和整合素β3 IOD值、MMP-8、VEGFA mRNA和蛋白相对表达水平、妊娠率和子宫胚胎数升高(P<0.05),另hAECs移植可改善子宫瘢痕大鼠子宫内膜组织病理形态,减轻子宫内膜纤维化程度。结论:hAECs移植可改善子宫内膜损伤,减少瘢痕形成,提高子宫内膜容受性,并增强模型大鼠的妊娠功能,其作用机制可能与促进MMP-8和VEGFA表达有关。

    Abstract:

    Objective: To investigate the effect of human amniotic epithelial cells (hAECs) transplantation on endometrium improvement and matrix metalloproteinase-8 (MMP-8) and vascular endothelial growth factor (VEGF) in a rat model of uterine scar. Methods: The uterine scar model of rats was established and randomly divided into model group and transplantation group, with 18 rats in each group. The other 18 rats were selected as sham operation group. The rats in the transplantation group were injected with hAECs in the scar of the uterus, and the rats in the model group and the sham operation group were only given the same amount of PBS. After 4 weeks, the uterine tissues of 8 rats in each group were collected and HE staining was used to observe the histomorphological changes, and the endometrial thickness and the number of glands were measured. Masson staining was used to observe endometrial fibrosis. Endometrial growth and receptivity were evaluated by immunohistochemical staining for cytokeratin and integrin β3, respectively. The mRNA expression levels of MMP-8 and VEGFA in endometrial tissues were detected by RT-qPCR. Western blotting was used to detect the protein expression levels of MMP-8 and VEGFA. After 8 weeks, the remaining 10 rats in each group were selected for gestational ability determination. Results: Compared with the sham-operation group, the endometrial thickness, the number of glands, the IOD value of keratin and integrin β3, the mRNA and protein relative expression levels of MMP-8 and VEGFA, the pregnancy rate and the number of uterine embryos in the model group and the transplantation group were significantly decreased (P<0.05). Compared with the model group, the endometrial thickness, the number of glands, the IOD value of keratin and integrin β3, the mRNA and protein relative expression levels of MMP-8 and VEGFA, the pregnancy rate and the number of uterine embryos were significantly increased in the transplantation group (P<0.05). In addition, hAECs transplantation could improve the pathological morphology of endometrial tissue in rats with uterine scar. Reduce the degree of endometrial fibrosis. Conclusion: hAECs transplantation could improve endometrial injury, reduce scar formation, improve endometrial receptivity, and enhance pregnancy function in model rats, which may be related to the promotion of MMP-8 and VEGFA expression.

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  • 收稿日期:2023-01-04
  • 最后修改日期:2023-06-12
  • 录用日期:2023-10-11
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