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不同类型巨噬细胞对细粒棘球蚴感染小鼠肝纤维化的影响。

Effect of different types of macrophages on hepatic fibrosis in Echinococcus Granulosus mice.

机构信息

Clinical Medical Research Institute, State Key Laboratory of Pathogenesis, Prevention, Treatment of Central Asian High Incidence Diseases, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China; College of Basic Medicine of Xinjiang Medical University, Urumqi, China.

Clinical Medical Research Institute, State Key Laboratory of Pathogenesis, Prevention, Treatment of Central Asian High Incidence Diseases, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China.

出版信息

Biomed Pharmacother. 2019 Sep;117:109178. doi: 10.1016/j.biopha.2019.109178. Epub 2019 Jul 1.

Abstract

OBJECTIVE

The purpose of this study is to illustrate the therapeutic effect of which kind of polarized macrophages-based cell therapy in hepatic fibrosis caused by cystic echinococcosis.

METHODS

The isolation culture and polarization induction of mouse bone marrow-derived macrophages (BMDM) are established in an in vitro environment. A model of Echinococcus granulosus infection is established by direct injection of the Echinococcus granulosus suspension into the left hepatic lobe. The macrophages are labeled in vitro and the localization of the returned macrophages in the liver of the mice is determined by in vivo tracing. Macrophages of different polarization types are injected into the successfully modeled mice through the tail vein, and the results of HE, Masson, Sirius Red, Desmin immunohistochemistry and Hyp content are inspected to evaluate by liver tissue. Liver pathology and changes in the degree of fibrosis.

RESULTS

Bone marrow-derived macrophages have been successfully obtained and induced into M1 and M2 macrophages by different conditions; a model of Echinococcus granulosus infection was successfully established. Macrophages labeled in vitro were returned to the model through the tail vein and they can be located in the liver; a variety of experimental results show that compared with the PBS group, the degree of fibrosis in the M0 group and the M1 group have been reduced, with statistical difference, and the M1 is better than M0 in terms of the therapeutic effect. There is no significant change in the degree of fibrosis in the M2 group.

CONCLUSION

Both M1 and M0 macrophages can alleviate liver fibrosis caused by persistent infection of Echinococcus granulosus, but the treatment effect of M1 macrophages is more significant. Cell therapy based on M1 macrophages may be a new idea for treating liver fibrosis caused by persistent infection of Echinococcus granulosus.

摘要

目的

本研究旨在阐明基于极化巨噬细胞的细胞治疗对肝包虫病纤维化的治疗效果。

方法

在体外环境中建立小鼠骨髓来源巨噬细胞(BMDM)的分离培养和极化诱导。通过直接将包虫混悬液注入左肝叶建立包虫感染模型。对体外标记的巨噬细胞进行体内示踪,确定其在小鼠肝脏中的定位。通过尾静脉将不同极化类型的巨噬细胞注入成功建模的小鼠体内,通过 HE、Masson、天狼猩红、结蛋白免疫组化和 Hyp 含量检查评估肝组织。观察肝组织病理及纤维化程度变化。

结果

成功获得骨髓来源巨噬细胞,并通过不同条件诱导为 M1 和 M2 巨噬细胞;成功建立包虫感染模型。体外标记的巨噬细胞通过尾静脉返回模型,可定位于肝脏;多种实验结果表明,与 PBS 组相比,M0 组和 M1 组的纤维化程度降低,差异有统计学意义,且 M1 组的治疗效果优于 M0 组。M2 组纤维化程度无明显变化。

结论

M1 和 M0 巨噬细胞均可减轻包虫持续感染引起的肝纤维化,但 M1 巨噬细胞的治疗效果更为显著。基于 M1 巨噬细胞的细胞治疗可能是治疗包虫持续感染引起肝纤维化的新思路。

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