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骨髓间充质干细胞对硫代乙酰胺诱导的大鼠肝纤维化的再生作用

Regenerative Effect of Bone Marrow-derived Mesenchymal Stem Cells in Thioacetamide-induced Liver Fibrosis of Rats.

作者信息

Mehrabani D, Khajehahmadi Z, Tajik P, Tamadon A, Rahmanifar F, Ashraf M, Tanideh N, Zare S

机构信息

Stem Cell Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran| Burn and Wound Healing Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

Comparative and Experimental Medicine Center, Shiraz University of Medical Sciences, Shiraz, Iran.

出版信息

Arch Razi Inst. 2019 Sep;74(3):279-286. doi: 10.22092/ari.2018.110029.1120. Epub 2019 Oct 1.

Abstract

The present study determined the regenerative effect of bone marrow-derived stem cells (BMSCs) on thioacetamide (TA)-induced liver fibrosis in rats. A total of 30 male Wistar rats were randomly divided into sham control and treatment groups. The rats of the sham control group were subdivided into three groups and sampled on the 14th, 18th, and 20th weeks after fibrosis induction. The rats of the treatment group were subdivided into two groups and sampled on the 4th and 6th weeks after BMSCs treatment. Fibrosis was induced by the intraperitoneal administration of 200 mg/kg of TA twice a week for a period of 14 weeks. All the animals underwent liver function tests and histopathologic evaluation 4 and 6 weeks after BMSCs transplantation. The BMSCs were characterized using osteogenic induction and reverse transcription-polymerase chain reaction. The BMSCs were plastic adherent, spindle-shaped, and positive for osteogenic differentiation. They expressed CD73 and were negative for CD45. The infiltration of inflammatory cells and deposition of collagen fibers were noticed after TA administration. A significant decline in inflammatory cells and a healing process were detected 4 weeks after cell transplantation. The amelioration in hepatic tissue was significant 6 weeks after cell therapy. Following the injection of BMSCs, a nonsignificant decrease was visible in aspartate transaminase level; however, this decline was significant for alanine aminotransferase level. The alkaline phosphatase and albumin levels showed an increasing trend after cell administration. The transplantation of BMSCs resulted in a significant regenerative effect after hepatic injuries. Therefore, it was shown that BMSCs transplantation can open a new window and be a therapy of choice in the amelioration of liver fibrosis.

摘要

本研究确定了骨髓来源的干细胞(BMSCs)对硫代乙酰胺(TA)诱导的大鼠肝纤维化的再生作用。总共30只雄性Wistar大鼠被随机分为假手术对照组和治疗组。假手术对照组的大鼠再分为三组,在纤维化诱导后的第14、18和20周进行取样。治疗组的大鼠再分为两组,在BMSCs治疗后的第4和6周进行取样。通过每周两次腹腔注射200mg/kg的TA,持续14周来诱导纤维化。在BMSCs移植后的第4和6周,所有动物均接受肝功能测试和组织病理学评估。使用成骨诱导和逆转录-聚合酶链反应对BMSCs进行鉴定。BMSCs呈贴壁生长,呈纺锤形,成骨分化呈阳性。它们表达CD73,而CD45呈阴性。TA给药后观察到炎性细胞浸润和胶原纤维沉积。细胞移植后4周检测到炎性细胞显著减少和愈合过程。细胞治疗后6周肝组织改善显著。注射BMSCs后,天冬氨酸转氨酶水平可见非显著下降;然而,这种下降对丙氨酸转氨酶水平而言是显著的。细胞给药后碱性磷酸酶和白蛋白水平呈上升趋势。BMSCs移植在肝损伤后产生了显著的再生作用。因此,表明BMSCs移植可为肝纤维化的改善开辟一个新的途径并成为一种首选治疗方法。

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