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人脐带间充质干细胞通过调节顺铂诱导损伤大鼠中基质金属蛋白酶-9/金属蛋白酶组织抑制因子-1的比例抑制子宫内膜纤维化来恢复子宫功能。

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

作者信息

Tang Yu, Si Yaru, Liu Chengen, Li Cui, Qu Li, Liu Ying, Fu Qiang, Luo Qianqian

机构信息

College of Basic Medicine, Binzhou Medical University, Yantai, Shandong 264003, China.

School of Pharmacology, Institute of Aging Medicine, Binzhou Medical University, Yantai, Shandong 264003, China.

出版信息

Stem Cells Int. 2023 Mar 20;2023:8014052. doi: 10.1155/2023/8014052. eCollection 2023.

Abstract

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. , uterine function in CDDP-induced injury rats was affected after hUMSC transplantation. , 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.

摘要

全球范围内,因化疗治愈癌症的育龄女性的生育能力正逐渐下降。顺铂(CDDP)作为临床上一种广谱化疗药物,其对女性生殖功能的损害不容忽视。目前,关于CDDP对子宫损伤的研究尚不充分,确切机制有待进一步探索。因此,我们开展此项研究,以确定人脐带间充质干细胞(hUMSCs)是否可改善CDDP诱导损伤大鼠的子宫损伤,并进一步探究其确切机制。通过腹腔注射CDDP建立CDDP诱导损伤大鼠模型,7天后经尾静脉注射hUMSCs。hUMSC移植后,CDDP诱导损伤大鼠的子宫功能受到影响。从细胞和蛋白水平进一步探究其具体机制。总体而言,CDDP诱导大鼠子宫功能障碍的具体原因是子宫内膜纤维化,hUMSC移植后该情况得到显著改善。机制研究发现,hUMSCs可调节CDDP损伤后子宫内膜基质细胞(EnSCs)中基质金属蛋白酶-9(MMP-9)/金属蛋白酶组织抑制剂-1(TIMP-1)的比例。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f0b/10042641/2f3c38a61101/SCI2023-8014052.001.jpg

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