[1]何煊,肇丽杰,隗洪进.hUC-MSCs调控PI3K/AKT通路对子宫瘢痕模型大鼠子宫内膜容受性及妊娠结局的影响[J].陕西医学杂志,2026,(2):159-165,174.[doi:DOI:10.3969/j.issn.1000-7377.2026.02.003]
　HE Xuan,ZHAO Lijie,KUI Hongjin.Effects of hUC-MSCs on endometrial receptivity and pregnancy outcomes in uterine scar model rats by regulating the PI3K/AKT pathway[J].,2026,(2):159-165,174.[doi:DOI:10.3969/j.issn.1000-7377.2026.02.003]
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hUC-MSCs调控PI3K/AKT通路对子宫瘢痕模型大鼠子宫内膜容受性及妊娠结局的影响

《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
期数:
2026年2期
页码:
159-165,174
栏目:
基础研究
出版日期:
2026-02-05

文章信息/Info

Title:
Effects of hUC-MSCs on endometrial receptivity and pregnancy outcomes in uterine scar model rats by regulating the PI3K/AKT pathway
作者:
何煊1; 2; 肇丽杰1; 隗洪进2
（1.广东医科大学第一临床医学院，广东 湛江524023；2.东莞市妇幼保健院妇科，广东 东莞 523000）
Author(s):
HE Xuan1; 2; ZHAO Lijie1; KUI Hongjin2
（1.The First Clinical Medical College of Guangdong Medical University,Zhanjiang 524023,China；2.Department of Gynecology,Dongguan Maternal and Child Health Care Hospital,Dongguan 523000,China)
关键词:
子宫瘢痕; 人脐带来源间充质干细胞; 磷脂酰肌醇3-激酶/蛋白激酶B通路; 子宫内膜容受性; 妊娠; 炎症反应; 纤维化
Keywords:
Uterine scar; Human umbilical cord-derived mesenchymal stem cells; Phosphoinositide 3-kinase/protein kinase B pathway; Endometrial receptivity; Pregnancy; Inflammatory response; Fibrosis
分类号:
R -33
DOI:
DOI:10.3969/j.issn.1000-7377.2026.02.003
文献标志码:
A
摘要:
目的：探讨人脐带来源间充质干细胞（hUC-MSCs）调控磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B（AKT）通路对子宫瘢痕模型大鼠子宫内膜容受性及妊娠结局的影响。方法：观察hUC-MSCs的形态特征并采用流式细胞术进行鉴定。选取雌性SD大鼠构建子宫瘢痕大鼠模型，并将建模成功的88只大鼠随机分为子宫瘢痕组、hUC-MSCs组、PI3K抑制剂（LY294002）组、hUC-MSCs+PI3K激活剂[重组大鼠胰岛素样生长因子-1（IGF-1）]组，每组22只。另选取22只雌性大鼠作为假手术组。hUC-MSCs组大鼠子宫瘢痕处注射50 μl PBS（含5×105个hUC-MSCs），腹腔注射10 ml/kg 0.9%氯化钠溶液；LY294002组大鼠腹腔注射10 mg/kg LY294002，子宫瘢痕处注射50 μl PBS；hUC-MSCs+IGF-1组大鼠子宫瘢痕处注射50 μl PBS（含5×105个hUC-MSCs），腹腔注射1.33 mg/kg IGF-1；子宫瘢痕组、假手术组大鼠子宫瘢痕处注射50 μl PBS，腹腔注射10 ml/kg 0.9%氯化钠溶液。采用HE、Masson染色分别检测子宫瘢痕处内膜组织病理学变化、纤维化程度；RT-qPCR检测子宫瘢痕处内膜组织转化生长因子-β1（TGF-β1）、Ⅰ型胶原蛋白（CollagenⅠ）和α-平滑肌肌动蛋白（α-SMA）mRNA表达；ELISA检测子宫瘢痕处内膜组织肿瘤坏死因子-α（TNF-α）、白细胞介素（IL）-1β、IL-6水平；免疫组织化学染色检测子宫瘢痕处内膜组织整合素β3、白血病抑制因子（LIF）表达；Western blot检测子宫瘢痕处内膜组织PI3K/AKT通路蛋白表达。选取同品系雄性大鼠50只，将雌鼠与性成熟雄鼠按1∶1合笼，记录大鼠妊娠率及子宫胚胎数。结果：显微镜观察细胞呈典型的成纤维细胞样、梭形贴壁生长。该细胞高表达间充质干细胞特异性表面标志物CD73、CD90和CD105，不表达造血系标志物CD34和CD45，符合hUC-MSCs特征。与假手术组比较，子宫瘢痕组子宫内膜组织呈蓝染色胶原沉积增多，腺体数、子宫内膜厚度、妊娠率、子宫胚胎数及子宫内膜组织中整合素β3和LIF平均光密度值降低，子宫内膜组织中TGF-β1、CollagenⅠ、α-SMA mRNA表达水平、TNF-α、IL-1β、IL-6水平及p-PI3K/PI3K、p-AKT/AKT比值升高（均P＜0.05）。与子宫瘢痕组比较，hUC-MSCs组、LY294002组呈蓝染色胶原沉积减少，腺体数、子宫内膜厚度、妊娠率、子宫胚胎数及子宫内膜组织中整合素β3、LIF平均光密度值升高，子宫内膜组织中TGF-β1、CollagenⅠ、α-SMA mRNA表达水平、TNF-α、IL-1β、IL-6水平及p-PI3K/PI3K、p-AKT/AKT比值降低（均P＜0.05）。IGF-1逆转了hUC-MSCs对子宫瘢痕模型大鼠上述指标的改善作用。结论：hUC-MSCs可能通过抑制PI3K/AKT通路逆转子宫内膜纤维化进程，减轻局部炎症反应，从而改善子宫瘢痕模型大鼠子宫内膜容受性及妊娠结局。
Abstract:
Objective:To investigate the effects of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) on endometrial receptivity and pregnancy outcomes in uterine scar model rats by regulating the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway.Methods：The morphological characteristics of hUC-MSCs were observed and identified by flow cytometry.A uterine scar rat model was established in female SD rats.A total of 88 rats with successful modeling were randomly divided into uterine scar group,hUC-MSCs group,PI3K inhibitor (LY294002) group and hUC-MSCs+PI3K activator (recombinant rat insulin-like growth factor-1 [IGF-1]) group,with 22 rats in each group.Another 22 female rats were selected as the sham operation group.In the hUC-MSCs group,50 μl of PBS containing 5×105 hUC-MSCs was injected into the uterine scar,and 10 ml/kg of 0.9% sodium chloride solution was injected intraperitoneally.In the LY294002 group,10 mg/kg of LY294002 was injected intraperitoneally,and 50 μl of PBS was injected into the uterine scar.In the hUC-MSCs+IGF-1 group,50 μl of PBS containing 5×105 hUC-MSCs was injected into the uterine scar,and 1.33 mg/kg of IGF-1 was injected intraperitoneally.In the uterine scar group and sham operation group,50 μl of PBS was injected into the uterine scar,and 10 ml/kg of 0.9% sodium chloride solution was injected intraperitoneally.HE and Masson staining were used to detect the pathological changes and fibrosis degree of endometrial tissue at the uterine scar.RT-qPCR was used to detect the mRNA expression of transforming growth factor-β1 (TGF-β1),collagen type Ⅰ (Collagen Ⅰ),and α-smooth muscle actin (α-SMA) in endometrial tissue at the uterine scar.ELISA was used to detect the levels of tumor necrosis factor-α (TNF-α),interleukin (IL)-1β,and IL-6 in endometrial tissue at the uterine scar.Immunohistochemical staining was used to detect the expression of integrin β3 and leukemia inhibitory factor (LIF) in endometrial tissue at the uterine scar.Western blot was used to detect the protein expression of the PI3K/AKT pathway in endometrial tissue at the uterine scar.Fifty male rats of the same strain were selected,and female rats were caged with sexually mature male rats at a ratio of 1∶1 to record the pregnancy rate and number of uterine embryos in rats.Results:Under the microscope,cells presented typical fibroblast-like,spindle-shaped adherent growth.These cells highly expressed the specific surface markers of mesenchymal stem cells CD73,CD90 and CD105,and did not express hematopoietic markers CD34 and CD45,which were consistent with the characteristics of hUC-MSCs.Compared with the sham operation group,the uterine scar group showed increased blue-stained collagen deposition in endometrial tissue,decreased number of glands,endometrial thickness,pregnancy rate,number of uterine embryos,and average optical density values of integrin β3 and LIF in endometrial tissue,and increased mRNA expression levels of TGF-β1,Collagen Ⅰ,and α-SMA,as well as levels of TNF-α,IL-1β and IL-6,and ratios of p-PI3K/PI3K and p-AKT/AKT in endometrial tissue (all P<0.05).Compared with the uterine scar group,the hUC-MSCs group and LY294002 group showed decreased blue-stained collagen deposition,increased number of glands,endometrial thickness,pregnancy rate,number of uterine embryos,and average optical density values of integrin β3 and LIF in endometrial tissue,and decreased mRNA expression levels of TGF-β1,Collagen Ⅰ,and α-SMA,as well as levels of TNF-α,IL-1β and IL-6,and ratios of p-PI3K/PI3K and p-AKT/AKT in endometrial tissue (all P<0.05).IGF-1 reversed the improvement effects of hUC-MSCs on the above indicators in the rat model of uterine scar.Conclusion:hUC-MSCs may reverse the endometrial fibrosis process and alleviate local inflammatory responses by inhibiting the PI3K/AKT pathway,thereby improving endometrial receptivity and pregnancy outcomes in uterine scar model rats.

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备注/Memo

备注/Memo:
广东省医学科学技术研究基金资助项目（A202112249）；广东省东莞市社会发展科技面上项目（20221800900582）
更新日期/Last Update: 2026-02-04