脂肪来源间充质干细胞治疗宫腔粘连的临床前研究  

Preclinical Study of Adipose-Derived Mesenchymal Stem Cells in the Treatment of Intrauterine Adhesions

作　　者：陈少蓉[1] 陈佳茗 赵云霞 高宏志[3] 张艾佳 施琦阳[1] CHEN Shaorong;CHEN Jiaming;ZHAO Yunxia;GAO Hongzhi;ZHANG Aijia;SHI Qiyang(Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou 362000, China;Department of Obstetrics and Gynecology, The University of Hong Kong-Shenzhen Hospital, Shenzhen 518053, China;Department of Neurosurgery, The Second Affiliated Hospital of Fujian Medical University, Quanzhou 362000, China;Provincial Clinical College of Fujian Medical University, Fuzhou 350001, China)

机构地区：[1]福建医科大学附属第二医院妇产科,泉州362000 [2]香港大学深圳医院妇产科,深圳518053 [3]福建医科大学附属第二医院神经外科,泉州362000 [4]福建医科大学省立临床医学院,福州350001

出　　处：《福建医科大学学报》2022年第1期12-18,共7页Journal of Fujian Medical University

基　　金：泉州市科技计划项目(2018N019S)。

摘　　要：目的探讨自体脂肪间充质干细胞(ADSCs)对宫腔粘连的修复作用及可能涉及的分子生物学机制。方法取C57BL-6雌性小鼠32只,分为4组,每组8只。假手术组剖腹后缝合,不接受治疗;磷酸盐缓冲液(PBS)模型组剖腹后在子宫壁反复搔刮20次进行建模,关腹后7 d再次开腹,双侧子宫角注射PBS 10μL;ADSCs组于建模7 d后再次开腹,双侧子宫角注射自体ADSCs;ADSCs+3D细胞水凝胶(ShakeGel^(TM)3D)组于建模7 d后,双侧子宫角注射ADSCs+ShakeGel^(TM)3D。治疗7 d后处死小鼠,收集双侧子宫,包埋切片后进行H-E和Masson染色,计算子宫内膜厚度、腺体数量和子宫内膜的纤维化面积,评价利用ADSCs和ADSCs+ShakeGel^(TM)3D治疗宫腔粘连的疗效。结果ADSCs组和ADSCs+ShakeGel^(TM)3D组小鼠的子宫内膜厚度和腺体数量明显增加,子宫内膜纤维化面积明显减少,α-平滑肌肌动蛋白(α-SMA)和转化生长因子-β1(TGF-β1)的表达水平降低,骨形态发生蛋白-7(BMP7)和Smad5的表达水平则提高。结论自体ADSCs和ADSCs+ShakeGel^(TM)3D可通过BMP7/Smad5通路增加子宫内膜的厚度和腺体的数量,并降低子宫内膜纤维化程度,促进子宫内膜组织修复,恢复其部分功能,起到治疗宫腔粘连的作用。Objective To investigate the repair effect of autologous adipose-derived mesenchymal stem cells(ADSCs)on intrauterine adhesions and the possible molecular biological mechanisms involved.Methods 32 female C57BL-6 mice were divided into 4 groups,8 in each group.The sham operation group was only sutured after laparotomy without treatment;after laparotomy,the mice in the PBS model group were repeatedly scratched 20 times in the uterine wall for modeling,and were reopened 7 days after closure.PBL 10μL was injected into bilateral uterine horns.The ADSCs group was reopened 7 days after modeling,and autologous ADSCs were injected into bilateral uterine horns;ADSCs+3D cell hydrogel(ShakeGel^(TM)3D)group was injected into bilateral uterine horns 7 days after modeling.After 7 days of treatment,the mice were sacrificed,and bilateral uterus were collected.H-E and Masson staining were performed after embedding sections.The thickness of endometrium,the number of glands and the fibrosis area of endometrium were calculated.The efficacy of ADSCs and ADSCs+ShakeGel^(TM)3D in the treatment of intrauterine adhesions was evaluated.Results The endometrial thickness and the number of glands in the autologous ADSCs and ADSCs+ShakeGel^(TM)3D treatment groups were significantly increased,the area of endometrial fibrosis was significantly reduced,the expression levels of alpha-smooth muscle actin(α-SMA)and transforming growth factor-beta1(TGF-β1)were decreased,and the expression levels of bone morphogenetic protein-7(BMP7)and Smad5 were increased.Conclusions Autologous ADSCs and ADSCs+ShakeGel^(TM)3D treatment can reduce the degree of endometrial fibrosis through the BMP7-Smad5 pathway,and promote endometrial tissue repair and partial functional recovery.

关 键 词：宫腔粘连 脂肪间充质干细胞 ShakeGel^(TM)3D BMP7/Smad5通路 

分 类 号：R71[医药卫生—妇产科学]