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壳寡糖减轻实验性自身免疫性前葡萄膜炎大鼠的眼部炎症。

Chitosan oligosaccharides attenuate ocular inflammation in rats with experimental autoimmune anterior uveitis.

作者信息

Fang I-Mo, Yang Chang-Hao, Yang Chung-May

机构信息

Department of Ophthalmology, Taipei City Hospital, Zhongxiao Branch, Taipei, Taiwan ; Department of Ophthalmology, National Taiwan University Hospital, No. 7, Chung-Shan S. Road, Taipei 10041, Taiwan.

Department of Ophthalmology, National Taiwan University Hospital, No. 7, Chung-Shan S. Road, Taipei 10041, Taiwan.

出版信息

Mediators Inflamm. 2014;2014:827847. doi: 10.1155/2014/827847. Epub 2014 Jul 24.

Abstract

We investigated the protective effects and mechanisms of chitosan oligosaccharides (COS) on experimental autoimmune anterior uveitis (EAAU) in rats. EAAU was induced in Lewis rats by footpad and intraperitoneal injections of melanin-associated antigen. The rats received intraperitoneal injections of low-dose (5 mg/kg) or high-dose (10 mg/kg) COS or PBS daily after the immunization. The effects of COS were evaluated by determining the clinical scores and the morphology of the iris/ciliary body (ICB). The expression of inflammatory mediators was evaluated using western blot, immunofluorescence, and ELISA. Treatment with COS significantly attenuated the clinical scores and the leukocyte infiltration in the ICB in a dose-dependent manner. COS effectively reduced the expression of inflammatory mediators (TNF-α, iNOS, MCP-1, RANTES, fractalkine, and ICAM-1). Moreover, COS decreased the IκB degradation and p65 presence in the ICB, which resulted in the inhibition of NF-κB/DNA binding activity. In an in vitro study, sensitized spleen-derived lymphocytes of the COS-treated group showed less chemotaxis toward their aqueous humor and decreased secretion of the above inflammatory mediators in the culture media. COS treated EAAU by inhibiting the activation of NF-κB and reducing the expression of inflammatory mediators. COS might be a potential treatment for acute anterior uveitis.

摘要

我们研究了壳寡糖(COS)对大鼠实验性自身免疫性前葡萄膜炎(EAAU)的保护作用及其机制。通过足垫和腹腔注射黑色素相关抗原来诱导Lewis大鼠发生EAAU。免疫后,大鼠每天腹腔注射低剂量(5 mg/kg)或高剂量(10 mg/kg)的COS或磷酸盐缓冲液(PBS)。通过测定临床评分以及虹膜/睫状体(ICB)的形态来评估COS的作用。使用蛋白质免疫印迹法、免疫荧光法和酶联免疫吸附测定法来评估炎症介质的表达。COS治疗以剂量依赖的方式显著减轻了临床评分以及ICB中的白细胞浸润。COS有效降低了炎症介质(肿瘤坏死因子-α、诱导型一氧化氮合酶、单核细胞趋化蛋白-1、调节激活正常T细胞表达和分泌因子、 fractalkine和细胞间黏附分子-1)的表达。此外,COS减少了ICB中IκB的降解和p65的存在,从而抑制了核因子-κB(NF-κB)/DNA结合活性。在一项体外研究中,COS处理组的致敏脾源性淋巴细胞对房水的趋化性降低,并且培养基中上述炎症介质的分泌减少。COS通过抑制NF-κB的激活和减少炎症介质的表达来治疗EAAU。COS可能是急性前葡萄膜炎的一种潜在治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2aff/4131455/56c6d5c2152f/MI2014-827847.001.jpg

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