脐带间充质干细胞移植预防宫腔粘连的研究
|
摘要
目的:采用机械刮宫建立大鼠宫腔粘连(IUA)模型,研究脐带间充质干细胞(UCMSCs)对IUA的预防作用。方法:将雌性未受孕SD大鼠麻醉后进行机械刮宫,分别于术后第3、5、7、9、12天进行大体观察,取子宫刮宫段,Western blot法检测TGF-β1表达,观察子宫内膜愈合情况。将雌性未受孕SD大鼠随机分为生理盐水组、干细胞组,麻醉后行机械刮宫,术后分别给药,于给药第3天打开腹腔进行大体观察,取刮宫段,Western blot法检测TGF-β1表达;常规固定组织后进行HE染色、Masson染色,观察受损子宫的愈合程度;免疫组化检测CD34和结缔组织生长因子(CTGF)的表达。结果:刮宫后第3天,与其余时间点相比,TGF-β1表达明显增加,IUA程度最为严重。与生理盐水组相比,干细胞组的IUA评分显著降低(P<0.05)。Western blot结果显示,与生理盐水组相比,干细胞组的TGF-β1表达明显降低,差异有统计学意义(P<0.01);HE染色、Masson染色显示,与生理盐水组相比,干细胞组的子宫内膜纤维化程度较低,内膜愈合较好。与生理盐水组相比,干细胞组子宫组织的CTGF染色分值明显下降(P<0.01),CD34染色分值明显升高(P<0.01)。结论:UCMSCs可有效预防术后IUA,促进子宫内膜愈合。
Objective:To establish a rat model of intrauterine adhesion by mechanical curettage,and to investigate the effect of umbilical cord mesenchymal stem cells(UCMSCs) on intrauterine adhesions.Methods:SD female rat without pregnancy were divided into two group:the control group and UCMSCs transplantation group.Mechanical curettage was used by self-made miniature curette to establish the rat model of intrauterine adhesion.HE staining,Masson staining,expression of transforming growth factor-β1(TGF-β1) by Western blot,The expressions of CD34 and Connective Tissue Growth Factor(CTGF) by IHC were used to evaluate the endometrial damage effect on the rats.Results:Compared with the control group,the degree of IUA was significantly improved in the transplantation group.The expression levels of TGF-β1 and CTGF of the transplantation group were lower than that of the control group,whereas the expression level of CD34 was higher than that of the control group(P<0.05).Conclusion:Umbilical cord mesenchymal stem cells may be useful to prevent IUA after uterine injury.
Objective:To establish a rat model of intrauterine adhesion by mechanical curettage,and to investigate the effect of umbilical cord mesenchymal stem cells(UCMSCs) on intrauterine adhesions.Methods:SD female rat without pregnancy were divided into two group:the control group and UCMSCs transplantation group.Mechanical curettage was used by self-made miniature curette to establish the rat model of intrauterine adhesion.HE staining,Masson staining,expression of transforming growth factor-β1(TGF-β1) by Western blot,The expressions of CD34 and Connective Tissue Growth Factor(CTGF) by IHC were used to evaluate the endometrial damage effect on the rats.Results:Compared with the control group,the degree of IUA was significantly improved in the transplantation group.The expression levels of TGF-β1 and CTGF of the transplantation group were lower than that of the control group,whereas the expression level of CD34 was higher than that of the control group(P<0.05).Conclusion:Umbilical cord mesenchymal stem cells may be useful to prevent IUA after uterine injury.
引文
[1] Deans R,Abbott J.Review of intrauterine adhesions[J].J Minim Invasive Gynecol,2010,17(5):555-569
[2] Yu D,Wong YM,Cheong Y,et al.Asherman syndrome-one century later[J].Fertil Steril,2008,89(4):759-779
[3] Yu D,Li TC,Xia E,et al.Factors affecting reproductive outcome of hysteroscopic adhesiolysis for Asherman's syndrome[J].Fertil Steril,2008,89(3):715-722
[4] Roy KK.Reproductive outcome following hysteroscopic adhesiolysis in patients with infertility due to Asherman's syndrome[J].Arch Gynecol Obstet,2010,281(2):355-361
[5] Pittenger MF,Mackay AM,Beck SC,et al.Multilineage potential Of adult human mesenchyma1 stem cells[J].Science,1999,284(5411):143-147
[6] 王改,贺斌,徐祥波,等.子宫内膜损伤与宫腔粘连动物模型的研究进展[J].生殖医学杂志,2014,23(10):856-859
[7] 张红红,李文.宫腔粘连的治疗策略及进展[J].中华生殖与避孕杂志,2018,28(3):248-251
[8] Romer,T,Schmidt T,Foth D.Pre- and postoperative hormonal treatment in patients with hysteroscopic surgery[J].Contrib Gynecol Obstet,2000,20(2):1-12
[9] Seo E,Wan Y,Kim J,et al.The Hippo-Salvador signaling pathway regulates renal tubulointerstitial fibrosis[J].Sci Rep,2016,6(1038):31931
[10] Jiang ZF,Shao LJ,Wang WM,et al.Decreased expression of Beclin-1 and LC3-II in human lung cancer[J].Mo Biol Rep,2012,39(1):259-267
[11] 吴圣,邵婧怡,王芳,等.PD-L1和PD-1在胃癌组织中的表达及其临床意义[J].安徽医科大学学报,2015,50(6):821-826
[12] Lei QY,Zhang H,Zhao B,et al.TAZ promotes cell proliferation and epithelial-mesenchymal transition and is inhibited by the hippo pathway[J].Mol Cell Biol,2008,28(7):2426-2436
[13] Shen X,Cheng S,Peng Y,et al.Attenuation of early liver fibrosis by herbal compound "Diwu Yanggan" through modulating the balance between epithelial-to-mesenchymal transition and mesenchymal-to-epithelial transition[J].BMC Complement Altern Med,2014,14:418
[14] Gargett CE,Ye L.Endometrial reconstruction from stem cells[J].Fertil Steril,2012,8(1):11-20
[15] 陈芳,隋龙.干细胞在宫腔粘连治疗中的研究进展[J].国际妇产科学杂志,2014,41(6):632-635
[16] Lapidot T,Dar A,Kollet O.How do stem cells find their way home?[J].Blood,2005,106(6):1901-1910
[17] Du HL,Taylor HS.Contribution of bone marrow-derived stem cells to endometrium and endometriosis[J].Stem Cell,2007,25(8):2082-2086
[18] 张颖,李娜,林筝,等.大鼠静脉多次注射人脐带间充质干细胞安全性的研究[J].心肺血管病杂志,2015,34(3):221-227
[19] 成九梅,靳琳,夏恩兰,等.雌孕激素受体及转化生长因子β1在宫腔粘连发病机制中的作用[J].中国实用妇科与产科杂志,2005,21(9):539-541
[2] Yu D,Wong YM,Cheong Y,et al.Asherman syndrome-one century later[J].Fertil Steril,2008,89(4):759-779
[3] Yu D,Li TC,Xia E,et al.Factors affecting reproductive outcome of hysteroscopic adhesiolysis for Asherman's syndrome[J].Fertil Steril,2008,89(3):715-722
[4] Roy KK.Reproductive outcome following hysteroscopic adhesiolysis in patients with infertility due to Asherman's syndrome[J].Arch Gynecol Obstet,2010,281(2):355-361
[5] Pittenger MF,Mackay AM,Beck SC,et al.Multilineage potential Of adult human mesenchyma1 stem cells[J].Science,1999,284(5411):143-147
[6] 王改,贺斌,徐祥波,等.子宫内膜损伤与宫腔粘连动物模型的研究进展[J].生殖医学杂志,2014,23(10):856-859
[7] 张红红,李文.宫腔粘连的治疗策略及进展[J].中华生殖与避孕杂志,2018,28(3):248-251
[8] Romer,T,Schmidt T,Foth D.Pre- and postoperative hormonal treatment in patients with hysteroscopic surgery[J].Contrib Gynecol Obstet,2000,20(2):1-12
[9] Seo E,Wan Y,Kim J,et al.The Hippo-Salvador signaling pathway regulates renal tubulointerstitial fibrosis[J].Sci Rep,2016,6(1038):31931
[10] Jiang ZF,Shao LJ,Wang WM,et al.Decreased expression of Beclin-1 and LC3-II in human lung cancer[J].Mo Biol Rep,2012,39(1):259-267
[11] 吴圣,邵婧怡,王芳,等.PD-L1和PD-1在胃癌组织中的表达及其临床意义[J].安徽医科大学学报,2015,50(6):821-826
[12] Lei QY,Zhang H,Zhao B,et al.TAZ promotes cell proliferation and epithelial-mesenchymal transition and is inhibited by the hippo pathway[J].Mol Cell Biol,2008,28(7):2426-2436
[13] Shen X,Cheng S,Peng Y,et al.Attenuation of early liver fibrosis by herbal compound "Diwu Yanggan" through modulating the balance between epithelial-to-mesenchymal transition and mesenchymal-to-epithelial transition[J].BMC Complement Altern Med,2014,14:418
[14] Gargett CE,Ye L.Endometrial reconstruction from stem cells[J].Fertil Steril,2012,8(1):11-20
[15] 陈芳,隋龙.干细胞在宫腔粘连治疗中的研究进展[J].国际妇产科学杂志,2014,41(6):632-635
[16] Lapidot T,Dar A,Kollet O.How do stem cells find their way home?[J].Blood,2005,106(6):1901-1910
[17] Du HL,Taylor HS.Contribution of bone marrow-derived stem cells to endometrium and endometriosis[J].Stem Cell,2007,25(8):2082-2086
[18] 张颖,李娜,林筝,等.大鼠静脉多次注射人脐带间充质干细胞安全性的研究[J].心肺血管病杂志,2015,34(3):221-227
[19] 成九梅,靳琳,夏恩兰,等.雌孕激素受体及转化生长因子β1在宫腔粘连发病机制中的作用[J].中国实用妇科与产科杂志,2005,21(9):539-541