研究动态
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hUMSC通过调节CDDP诱导损伤大鼠中MMP-9/TIMP-1比例,抑制子宫内膜纤维化,从而恢复子宫功能。

hUMSCs Restore Uterine Function by Inhibiting Endometrial Fibrosis via Regulation of the MMP-9/TIMP-1 Ratio in CDDP-Induced Injury Rats.

发表日期:2023
作者: Yu Tang, Yaru Si, Chengen Liu, Cui Li, Li Qu, Ying Liu, Qiang Fu, Qianqian Luo
来源: CLINICAL PHARMACOLOGY & THERAPEUTICS

摘要:

接受化疗治疗后康复的育龄女性的生育能力在全球范围内逐渐下降。作为一种广谱化疗药物,在临床上,顺铂(CDDP)对女性生殖功能的损伤不容忽视。目前,CDDP对子宫损伤的研究还不足,需要进一步探索其确切机制。因此,我们进行了这项研究,旨在确定是否可以通过注入人脐带间充质干细胞(hUMSCs)来改善CDDP诱导损伤大鼠的子宫损伤,并进一步探索其确切机制。通过腹腔注射CDDP建立了损伤大鼠模型,七天后尾静脉注射hUMSCs。在体内,CDDP诱导损伤大鼠的子宫功能受到了hUMSC移植的影响。在体外,从细胞和蛋白质水平进一步探索了具体机制。总体而言,CDDP诱导的大鼠子宫功能障碍的具体原因是子宫内膜纤维化,在hUMSC移植后得到了明显的改善。进一步的研究发现,CDDP损伤后,hUMSCs可以调节内膜基质细胞中基质金属蛋白酶-9(MMP-9)/组织金属蛋白酶抑制剂-1(TIMP-1)的比例。版权所有 © 2023 Yu Tang等。
The fertility of females of childbearing age who are cured of cancer by chemotherapy is gradually declining globally. As a broad-spectrum chemotherapy drug in clinic, the damage of cisplatin (CDDP) to female reproductive function cannot be ignored. At present, the study of CDDP damage to the uterus is not sufficient, and the exact mechanism needs to be further explored. Therefore, we conducted this research to determine whether uterine injury in CDDP-induced injury rats might be improved by human umbilical cord mesenchymal stem cells (hUMSCs) and to further explore the precise mechanism. The rat model of CDDP-induced injury was established by intraperitoneal injection of CDDP, and hUMSCs were injected into the tail vein 7 days later. In vivo, uterine function in CDDP-induced injury rats was affected after hUMSC transplantation. In vitro, the specific mechanism was further explored from the cell and protein levels. Overall, the specific reason of CDDP-induced uterine dysfunction in rats was endometrial fibrosis, which was significantly improved after hUMSC transplantation. Further investigation of the mechanism found that hUMSCs could regulate the ratio of matrix metalloproteinase-9 (MMP-9)/tissue inhibitor of metalloproteinase-1 (TIMP-1) in endometrial stromal cells (EnSCs) after CDDP injury.Copyright © 2023 Yu Tang et al.