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骨髓间充质干细胞在胆道闭锁小鼠中的抗纤维化潜力。

Antifibrotic potential of bone marrow‑derived mesenchymal stem cells in biliary atresia mice.

机构信息

Department of General Surgery, Jiangxi Provincial Children's Hospital, Nanchang, Jiangxi 330006, P.R. China.

Department of Ultrasound, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi 330006, P.R. China.

出版信息

Mol Med Rep. 2018 Oct;18(4):3983-3988. doi: 10.3892/mmr.2018.9353. Epub 2018 Aug 3.

DOI:10.3892/mmr.2018.9353
PMID:30106103
Abstract

Biliary atresia (BA) is a rare and severe disease that affects infants where a fibroinflammatory process destroys the bile ducts, leading to fibrosis and biliary cirrhosis, and mortality if untreated. Bone marrow‑derived mesenchymal stem cells (BMMSCs) have been considered as a promising therapy in fibrotic diseases. The aim of the present was to investigate the anti‑fibrotic roles of BMMSC transplantation in a BA mouse model. Mouse BA models were established by Rhesus rotavirus administration to neonatal mice. The results revealed that the liver enzyme and bilirubin metabolism levels, and the levels of the oxidative stress marker malondialdehyde (MDA) and the fibrosis marker were all increased in the BA model, while the liver tissue levels of superoxide dismutase and glutathione peroxidase were reduced. The hematoxylin and eosin and Masson's trichrome staining revealed severe liver fibrosis and collagen accumulation in BA livers. However, these indicators were all reversed once the BA mice were administered the BMMSC inoculation. In conclusion, the present study demonstrated the anti‑fibrotic potential of BMMSCs in BA mice, which may provide a novel approach to ameliorate the fibrotic response in BA patients.

摘要

先天性胆道闭锁(BA)是一种罕见且严重的疾病,会影响婴儿,其中纤维炎症过程会破坏胆管,导致纤维化和胆汁性肝硬化,如果不治疗则会导致死亡。骨髓间充质干细胞(BMMSC)已被认为是纤维性疾病的一种有前途的治疗方法。本研究旨在探讨 BMMSC 移植在 BA 小鼠模型中的抗纤维化作用。通过向新生小鼠给予恒河猴轮状病毒建立 BA 小鼠模型。结果显示,BA 模型中的肝酶和胆红素代谢水平以及氧化应激标志物丙二醛(MDA)和纤维化标志物的水平均升高,而肝组织中超氧化物歧化酶和谷胱甘肽过氧化物酶的水平降低。苏木精和伊红及 Masson 三色染色显示 BA 肝脏中有严重的肝纤维化和胶原积聚。然而,一旦 BA 小鼠接受 BMMSC 接种,这些指标均得到逆转。综上所述,本研究证明了 BMMSC 在 BA 小鼠中的抗纤维化潜力,这可能为改善 BA 患者的纤维化反应提供一种新方法。

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引用本文的文献

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Med Rev (2021). 2024 Jul 1;4(4):326-365. doi: 10.1515/mr-2024-0029. eCollection 2024 Aug.
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Cellular Therapies in Pediatric Liver Diseases.儿童肝脏疾病的细胞治疗。
Cells. 2022 Aug 10;11(16):2483. doi: 10.3390/cells11162483.
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Pediatric Cholestatic Liver Disease: Review of Bile Acid Metabolism and Discussion of Current and Emerging Therapies.
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Front Med (Lausanne). 2020 May 5;7:149. doi: 10.3389/fmed.2020.00149. eCollection 2020.
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Preclinical insights into cholangiopathies: disease modeling and emerging therapeutic targets.胆管疾病的临床前研究进展:疾病建模与新兴治疗靶点
Expert Opin Ther Targets. 2019 Jun;23(6):461-472. doi: 10.1080/14728222.2019.1608950. Epub 2019 Apr 22.