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海胆色素海胆紫酮治疗大鼠内毒素诱导性葡萄膜炎的疗效

Amelioration of endotoxin-induced uveitis treated with the sea urchin pigment echinochrome in rats.

作者信息

Lennikov Anton, Kitaichi Nobuyoshi, Noda Kousuke, Mizuuchi Kazuomi, Ando Ryo, Dong Zhenyu, Fukuhara Junichi, Kinoshita Satoshi, Namba Kenichi, Ohno Shigeaki, Ishida Susumu

机构信息

Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.

Department of Ocular Inflammation and Immunology, Hokkaido University Graduate School of Medicine, Sapporo, Japan ; Department of Ophthalmology, Health Sciences University of Hokkaido, Sapporo, Japan.

出版信息

Mol Vis. 2014 Feb 7;20:171-7. eCollection 2014.

Abstract

PURPOSE

Echinochrome is a pigment present in the shells and spines of sea urchins. It has been reported to have several biologic protective effects, including in experimental models of myocardial ischemia/reperfusion injury, for which the proposed mechanisms are scavenging reactive oxygen species (ROS) and chelating iron. Endotoxin-induced uveitis (EIU) is an animal model of acute anterior segment intraocular inflammation that is induced by the injection of lipopolysaccharide (LPS). In this study, the therapeutic effect of echinochrome was examined in uveitis using the EIU model.

METHODS

EIU was induced in Lewis rats via 200 μg subcutaneous injections of LPS from Escherichia coli. Echinochrome was administered intravenously in 10, 1, or 0.1 mg/kg doses suspended in PBS (controls were injected with PBS only). Twenty-four hours after LPS injection, the number of infiltrating cells and the protein concentration in aqueous humor were determined. Aqueous tumor necrosis factor α (TNF-α) concentration was quantified with enzyme-linked immunosorbent assay, eyes were stained with nuclear factor (NF) κB antibodies, and ROS production was determined by dihydroethidium staining in fresh frozen samples.

RESULTS

The number of inflammatory aqueous cells and protein levels were lower in the groups treated with 10 and 1 mg/kg of echinochrome than in the untreated LPS group (p<0.01). Treatment with 10 and 1 mg/kg of echinochrome significantly reduced TNF-α concentrations in aqueous humor (p<0.01). The numbers of NFκB-positive cells and ROS signals were also reduced by echinochrome administration (p<0.05).

CONCLUSIONS

Echinochrome ameliorated intraocular inflammation caused by EIU by reducing ROS production, thereby also decreasing the expression of NFκB and TNF-α. As a natural pigment, echinochrome may therefore be a promising candidate for the safe treatment of intraocular inflammation. The use of sea urchin shells and spines in health foods and medical products is thus both economically and environmentally meaningful.

摘要

目的

海胆色素是存在于海胆壳和刺中的一种色素。据报道,它具有多种生物保护作用,包括在心肌缺血/再灌注损伤的实验模型中,其提出的机制是清除活性氧(ROS)和螯合铁。内毒素诱导的葡萄膜炎(EIU)是一种急性眼前节眼内炎症的动物模型,由注射脂多糖(LPS)诱导。在本研究中,使用EIU模型研究了海胆色素对葡萄膜炎的治疗效果。

方法

通过皮下注射200μg大肠杆菌LPS在Lewis大鼠中诱导EIU。将海胆色素以10、1或0.1mg/kg的剂量静脉注射,悬浮于PBS中(对照组仅注射PBS)。LPS注射后24小时,测定房水中浸润细胞数量和蛋白质浓度。用酶联免疫吸附测定法定量房水中肿瘤坏死因子α(TNF-α)浓度,用核因子(NF)κB抗体对眼睛进行染色,并通过二氢乙锭染色在新鲜冷冻样品中测定ROS产生。

结果

用10mg/kg和1mg/kg海胆色素治疗的组中,炎性房水细胞数量和蛋白质水平低于未治疗的LPS组(p<0.01)。用10mg/kg和1mg/kg海胆色素治疗可显著降低房水中TNF-α浓度(p<0.01)。给予海胆色素也减少了NFκB阳性细胞数量和ROS信号(p<0.05)。

结论

海胆色素通过减少ROS产生改善了EIU引起的眼内炎症,从而也降低了NFκB和TNF-α的表达。因此,作为一种天然色素,海胆色素可能是安全治疗眼内炎症的有前途的候选物。因此,在保健食品和医疗产品中使用海胆壳和刺在经济和环境方面都具有意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3b3/3919668/c915f8f1635d/mv-v20-171-f1.jpg

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