人脐带来源的мesenchymal基质细胞减轻脂多糖诱导的大鼠肝损伤

Q4 Medicine
O. Redko, A. Dovgalyuk, Z. Nebesna, S. Kramar, A. Sverstyuk, M. Korda
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引用次数: 0

摘要

急性呼吸窘迫综合征(ARDS)是一种严重的临床疾病,可导致包括肝损伤在内的多器官功能障碍。人脐带来源的间充质基质细胞(hUC-MSCs)由于其分化为各种细胞类型的能力及其抗炎和免疫调节特性,已被证明对多种疾病具有治疗潜力。目的:探讨hUC-MSCs对脂多糖(LPS)诱导的大鼠肝损伤的治疗作用。材料和方法:72只成年雄性Wistar大鼠随机分为9组:对照组、鼻内注射LPS后3天、7天和28天、LPS 24小时和hUC MSCs 2天、LPS 4天和hUC MSC 3天、LPS 14天和hUC-MSCs 14天、LPS 21天和hUC-MSCs 7天,以及对照组。使用胶原酶I酶消化法从人脐带组织中分离MSC。hUC MSC以1∙106个细胞/kg体重的剂量腹膜内注射。采用动力学方法测定血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶和碱性磷酸酶(ALP)水平。通过苏木精和伊红染色切片的组织学评分分析肝细胞坏死、肝结构损伤、肝细胞空泡化、炎症和弥漫性血管内凝血(DIC)的水平。应用免疫组织化学方法检测肝组织中TGF-β1的表达。结果:临床前研究表明,hUC-MSCs治疗可显著改善大鼠的肝功能,减轻LPS诱导的肝损伤。与未治疗组相比,hUC-MSCs治疗组的肝细胞坏死、肝结构损伤、肝细胞空泡化、炎症、DIC迹象、纤维化以及血清肝标志物ALT、AST和ALP水平降低证明了这一点。研究还表明,在肝损伤的早期阶段,使用hUC-MSCs更有效。结论:我们的研究结果表明,hUC-MSCs疗法可能有望成为LPS诱导的肝损伤的潜在治疗方法。需要进一步的研究来更好地了解潜在的机制,并确定hUC MSCs治疗在临床实践中的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Human umbilical cord-derived мesenchymal stromal cells mitigate lipopolysaccharide-induced liver injury in rats
Acute Respiratory Distress Syndrome (ARDS) is a severe clinical condition that can cause multi-organ dysfunction, including liver injury. Human umbilical cord-derived mesenchymal stromal cells (hUC-MSCs) have been shown to possess therapeutic potential for a variety of diseases due to their ability to differentiate into various cell types and their anti-inflammatory and immunomodulatory properties. Purpose: To investigate the potential of hUC-MSCs for treating lipopolysaccharide (LPS)-induced liver injury in rats. Materials and methods: 72 mature male Wistar rats were randomly assigned to nine groups: control, 3 days, 7 days, and 28 days after intranasal administration of LPS, 24 hours of LPS and 2 days of hUC-MSCs, 4 days of LPS and 3 days of hUC-MSCs, 14 days of LPS and 14 days of hUC-MSCs, 21 days of LPS and 7 days of hUC-MSCs injection, and control 3 days after hUC-MSCs injection. The isolation of MSCs from human umbilical cord tissue was performed using an enzymatic digestion method with collagenase I. hUC-MSCs were injected intraperitoneally at a dose of 1∙106 cells/kg body weight. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were measured using the kinetic method. The levels of hepatocellular necrosis, liver structural damage, hepatocyte vacuolation, inflammation and disseminated intravascular coagulation (DIC) were analyzed by histological scoring of sections stained with hematoxylin and eosin. The expression of TGF-β1 in the liver tissue was evaluated by immunohistochemistry. Results: The preclinical study demonstrated that treatment with hUC-MSCs significantly improved liver function and attenuated LPS-induced liver injury in rats. This was evidenced by a reduction in hepatocellular necrosis, liver structural damage, hepatocyte vacuolation, inflammation, signs of DIC, fibrosis and lower levels of serum liver markers ALT, AST and ALP in the hUC-MSCs-treated groups compared to the untreated groups. The study also revealed that the use of hUC-MSCs was more effective at the earlier stage of liver injury. Conclusions: Our findings suggest that hUC-MSCs therapy may hold promise as a potential treatment for LPS-induced liver injury. Further research is needed to better understand the underlying mechanisms and to determine the potential for hUC-MSCs therapy in clinical practice.
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来源期刊
Cell and Organ Transplantology
Cell and Organ Transplantology Medicine-Transplantation
CiteScore
0.40
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8
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