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

Chitosan oligosaccharides attenuate ocular inflammation in rats with experimental autoimmune anterior uveitis.
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DOI:
10.1155/2014/827847
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发表时间:
2014
影响因子:
4.6
通讯作者:
Yang CM
Yang CM
中科院分区:
医学3区
文献类型:
--
作者:
Fang IM;Yang CH;Yang CM

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探讨壳寡糖(COS)对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诱导Lewis大鼠EAAU。免疫后每天分别给予低剂量(5 mg/kg)或高剂量(10 mg/kg)的黄曲霉毒素或硫代巴比妥钠或硫代巴比妥钠。通过临床评分和虹膜/睫状体(ICB)的形态观察来评价COS的疗效。用免疫印迹、免疫荧光和酶联免疫吸附试验检测炎性介质的表达。COS治疗可明显减轻ICB的临床评分和白细胞浸润,并呈剂量依赖关系。COS可有效减少炎症介质(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、RANTES、Fractalkine和ICAM-1)的表达。此外,COS还降低了I-κB的降解和p65在ICB中的存在,从而抑制了NF-κB/DNA结合活性。在体外研究中,COS处理组的致敏脾淋巴细胞对房水的趋化作用较弱,培养上清液中上述炎症介质的分泌减少。COS通过抑制NF-κB的活化,减少炎性介质的表达来治疗急性胰腺炎。COS可能是治疗急性前葡萄膜炎的一种潜在方法。
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.
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