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载铁蛋白纳米颗粒可减少感染并改善感染利什曼原虫的小鼠的免疫功能。

Ferroportin-encapsulated nanoparticles reduce infection and improve immunity in mice infected with Leishmania major.

机构信息

Immunology Department, Pasteur Institute of Iran, Tehran, Iran; Marine Biology Department, Sciences & Research Branch, Islamic Azad University, Hesarak, Iran.

Immunology Department, Pasteur Institute of Iran, Tehran, Iran.

出版信息

Int J Pharm. 2014 May 15;466(1-2):375-81. doi: 10.1016/j.ijpharm.2014.03.039. Epub 2014 Mar 20.

Abstract

Inoculation of inbred mice by Leishmania major results in two different patterns. C57BL/6 mice display resistance against L. major but BALB/c mice show susceptibility to L. major with visceral infection, anemia and death. In this study, the effects of treatment of L. major-infected BALB/c mice with a ferroportin (Fpn)-encoding construct via nanoparticles were evaluated. A fragment encoding Fpn, a major regulator of iron homeostasis, was amplified and sub-cloned to a GFP expression vector to express Fpn-EGFP protein. This construct was incorporated in nanoparticles of alginate/chitosan polymers and orally administered to L. major-infected BALB/c mice. Blood hematocrit and iron, footpad size, parasite load and concentration of IFNG, IL4 and IL10 by ELISA were measured in the treated and untreated mice. The results indicated that the treated mice had significantly higher hematocrit and iron levels while exhibited significantly lower footpad size and parasite load measurements. Moreover, lower levels of IL4 and IL10 and higher ratios of IFNG/IL4 or IFNG/IL10 were shown in the treated, compared to the untreated mice. In conclusion, treating BALB/c mice infected with L. major with encapsulated Fpn-encoding construct in alginate/chitosan nanoparticles were shown to reduce the infection and improve anemia and immunity in the animal model of leishmaniasis.

摘要

经内源性感染的近交系小鼠接种利什曼原虫主要会产生两种不同的模式。C57BL/6 小鼠对利什曼原虫表现出抗性,但 BALB/c 小鼠对利什曼原虫表现出易感性,伴有内脏感染、贫血和死亡。在这项研究中,评估了通过纳米颗粒对感染利什曼原虫的 BALB/c 小鼠用铁蛋白(Fpn)编码构建体进行治疗的效果。扩增并亚克隆编码铁稳态主要调节剂 Fpn 的片段到 GFP 表达载体以表达 Fpn-EGFP 蛋白。该构建体被包裹在藻酸盐/壳聚糖聚合物的纳米颗粒中,并通过口服给予感染利什曼原虫的 BALB/c 小鼠。通过 ELISA 测量治疗和未治疗小鼠的血液血细胞比容和铁、足垫大小、寄生虫负荷以及 IFNG、IL4 和 IL10 的浓度。结果表明,治疗组小鼠的血细胞比容和铁水平明显升高,而足垫大小和寄生虫负荷明显降低。此外,与未治疗的小鼠相比,治疗组的 IL4 和 IL10 水平较低,IFNG/IL4 或 IFNG/IL10 的比值较高。总之,用藻酸盐/壳聚糖纳米颗粒包裹 Fpn 编码构建体治疗感染利什曼原虫的 BALB/c 小鼠可减少感染,并改善动物模型中的贫血和免疫。

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