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人脐带间充质干细胞和小鼠骨髓细胞抗肝纤维化作用及其机制的研究。

Anti-fibrotic potential of human umbilical cord mononuclear cells and mouse bone marrow cells in CCl- induced liver fibrosis in mice.

机构信息

Pharmacology and Toxicology Department, Faculty of Pharmacy, Tanta University, Tanta, Egypt.

Zoology Department, Faculty of Science, Immunology and Biotechnology Unit, Immunology and Biotechnology Division, Center of Excellence in Cancer Research, Tanta University, Tanta, Egypt.

出版信息

Biomed Pharmacother. 2017 May;89:1378-1386. doi: 10.1016/j.biopha.2017.03.007. Epub 2017 Mar 19.

Abstract

Liver fibrosis is the consequence of hepatocyte injury that leads to the activation of hepatic stellate cells (HSC). The treatment of choice is Liver transplantation; however, it has many problems such as surgery-related complications, immunological rejection and high costs associated with the procedure. Stem cell-based therapy would be a potential alternative, so the aim of this study is to investigate the therapeutic potential of human umbilical cord mononuclear cells (MNC) and mouse bone marrow cells (BMC) against carbon tetrachloride (CCl) induced liver fibrosis in mice and compare it with that of silymarin. In the present study, male albino mice (N=60) were divided into six groups (10 mice each), the first group served as the normal control group while the remaining five groups were rendered fibrotic by intraperitoneal injections of CCl and being left for 6 weeks to develop hepatic fibrosis. Thereafter, the mice were divided into CCl group, CCl group receiving MNC or BMC or silymarin or MNC and silymarin combination. After the specified treatment period, animals were then euthanized, blood and tissue samples were collected for measurement of alanine aminotransferase(ALT), aspartate aminotransferase(AST), malondialdehyde(MDA), reduced glutathione(GSH), collagen, Laminin, transforming growth factor β1(TGFβ1), tumor necrosis factor alpha(TNFα). MNC, BMC, and the combination therapy showed a significant decrease in ALT, AST, MDA, collagen, Laminin, TGFβ1, and TNFα and a significant increase in GSH. The data displayed a similar regression of fibrosis with the histological and immunohistological parameters. In conclusion, MNC, BMC and the combination therapy showed a potential therapeutic effect against liver fibrosis via reducing oxidative stress, inflammatory mediators, and fibrogenic markers.

摘要

肝纤维化是肝细胞损伤导致肝星状细胞(HSC)激活的结果。治疗的首选方法是肝移植;然而,它存在许多问题,如与手术相关的并发症、免疫排斥和程序相关的高成本。基于干细胞的治疗将是一种潜在的替代方法,因此本研究旨在研究人脐带单核细胞(MNC)和小鼠骨髓细胞(BMC)对四氯化碳(CCl)诱导的小鼠肝纤维化的治疗潜力,并将其与水飞蓟素进行比较。在本研究中,雄性白化小鼠(N=60)分为六组(每组 10 只),第一组作为正常对照组,其余五组通过腹腔注射 CCl 致纤维化,并留作 6 周以发展肝纤维化。此后,将小鼠分为 CCl 组、CCl 组接受 MNC 或 BMC 或水飞蓟素或 MNC 和水飞蓟素联合治疗。指定治疗期结束后,处死动物,采集血液和组织样本,用于测量丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、丙二醛(MDA)、还原型谷胱甘肽(GSH)、胶原、层粘连蛋白、转化生长因子β1(TGFβ1)、肿瘤坏死因子α(TNFα)。MNC、BMC 和联合治疗组 ALT、AST、MDA、胶原、层粘连蛋白、TGFβ1 和 TNFα 显著降低,GSH 显著增加。数据显示,纤维化的组织学和免疫组织化学参数也有类似的回归。总之,MNC、BMC 和联合治疗通过降低氧化应激、炎症介质和纤维生成标志物显示出对肝纤维化的潜在治疗作用。

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