Effective treatment with oral administration of rebamipide in a mouse model of Sjogren's syndrome
Effective treatment with oral administration of rebamipide in a mouse model of Sjogren's syndrome
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DOI：
10.1002/art.23163
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发表时间：
2008-02-01
影响因子：
--
通讯作者：
Hayashi, Yoshio
中科院分区：
文献类型：
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作者：
Kohashi, Masayuki;Ishimaru, Naozumi;Hayashi, Yoshio
Objective.在干燥综合征（SS）的NFS/sld小鼠模型中确定口服给予粘膜保护剂瑞巴派特（rebamipide）是否有效治疗该疾病。从4周龄开始至8周龄，每天给予NFS/sld小鼠口服剂量的瑞巴派特（0.3mg/kg体重或3 mg/kg）或单独的媒介物。在治疗期间和治疗后监测唾液和泪液的体积。最后一次给药后，检查组织的组织学特征、受影响腺体中TUNEL+凋亡导管细胞、T细胞和细胞因子功能以及免疫球蛋白同种型和血清自身抗体水平。3 mg/kg剂量的瑞巴派特可预防自身免疫性病变的发展。瑞巴派特治疗小鼠的平均唾液体积显著高于对照小鼠。我们发现，与对照组小鼠相比，瑞巴派特治疗组小鼠的唾液腺和泪腺中TUNEL+凋亡导管细胞减少。瑞巴派特治疗抑制了与受损NF-κ B活性相关的CD 4 + T细胞和Th 1细胞因子（白细胞介素-2、干扰素-γ）的活化。血清自身抗体、IgM和IgG 1的产生明显受到抑制。我们的研究结果表明，口服瑞巴派特治疗SS的疗效。瑞巴派特代表了一种新的治疗策略，用于治疗SS引起的干燥症状患者以及其他疾病患者。
Objective. To determine whether oral administration of rebamipide, a mucosal protective agent, is effective in the treatment of Sjogren's syndrome (SS) in the NFS/sld mouse model of the disease.Methods. NFS/sld mice were given daily oral doses of rebamipide (0.3 mg/kg of body weight or 3 mg/kg) or vehicle alone starting from the age of 4 weeks to the age of 8 weeks. The volume of saliva and tears was monitored during and after treatment. After the final dose, histologic features of the tissues, TUNEL+ apoptotic duct cells in affected glands, T cell and cytokine function, and levels of immunoglobulin isotypes and serum autoantibodies were examined.Results. The 3-mg/kg dose of rebamipide prevented the development of autoimmune lesions. The average volume of saliva in rebamipide-treated mice was significantly higher than that in control mice. We found decreased TUNEL+ apoptotic duct cells in the salivary and lacrimal glands of rebamipide-treated mice as compared with control mice. Rebamipide treatment suppressed the activation of CD4+ T cells and Th1 cytokines (interleukin-2, interferon-gamma) associated with impaired NF-kappa B activity. Production of serum autoantibodies, IgM, and IgG1 was clearly inhibited.Conclusion. Our findings demonstrate the efficacy of oral administration of rebamipide in the treatment of SS. Rebamipide represents a new therapeutic strategy for the treatment of patients with sicca symptoms caused by SS, as well as for patients with other diseases.