GABA Administration Ameliorates Sjogren's Syndrome in Two Different Mouse Models.
GABA Administration Ameliorates Sjogren's Syndrome in Two Different Mouse Models.
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γ-氨基丁酸（GABA）给药改善两种不同小鼠模型中的干燥综合征。
DOI：
10.3390/biomedicines10010129
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发表时间：
2022-01-07
期刊：
影响因子：
4.7
通讯作者：
Kaufman DL
中科院分区：
文献类型：
--
作者：
Song M;Tian J;Middleton B;Nguyen CQ;Kaufman DL
干燥综合征（SS）是一种慢性自身免疫性疾病，其特征是唾液腺和泪腺中出现淋巴细胞浸润，导致口腔和眼部干燥。目前临床上没有被批准的可延缓SS进展的疗法。免疫细胞拥有神经递质γ-氨基丁酸（GABA）的受体（GABA - Rs），并且这些受体的激活具有免疫调节作用。我们在两种自发性SS模型——NOD.B10 - H2b和C57BL/6.NOD - Aec1Aec2小鼠中测试了给予GABA是否有可能改善SS。口服GABA治疗在以下两种情况下启动：（1）在涎腺炎发生之后但在明显症状出现之前；（2）在明显症状出现之后。数周后评估发现，在两种SS小鼠模型中，GABA治疗的小鼠唾液和泪液分泌量更多，唾液流出时间也更快。在明显疾病发作后开始GABA治疗时，这种效果尤其明显。这种外分泌功能的保留并没有伴随着GABA治疗小鼠唾液腺或泪腺中淋巴细胞病灶数量或面积的显著变化，我们对这些观察结果的可能原因进行了讨论。鉴于GABA治疗保留了唾液和泪液的分泌（这是SS最显著的症状）且食用安全，它可能为帮助改善SS提供一种新的方法。
Sjögren’s syndrome (SS) is a chronic autoimmune disease characterized by lymphocytic infiltrates in the salivary and lachrymal glands resulting in oral and ocular dryness. There are no clinically approved therapies to slow the progression of SS. Immune cells possess receptors for the neurotransmitter GABA (GABA-Rs) and their activation has immunoregulatory actions. We tested whether GABA administration has potential for amelioration of SS in NOD.B10-H2b and C57BL/6.NOD-Aec1Aec2 mice, two spontaneous SS models. Oral GABA treatment was initiated (1) after the development of sialadenitis but before the onset of overt symptoms, or (2) after the appearance of overt symptoms. When assessed weeks later, GABA-treated mice had greater saliva and tear production, as well as quicker times to salvia flow, in both SS mouse models. This was especially evident when GABA treatment was initiated after the onset of overt disease. This preservation of exocrine function was not accompanied by significant changes in the number or area of lymphocytic foci in the salivary or lachrymal glands of GABA-treated mice and we discuss the possible reasons for these observations. Given that GABA-treatment preserved saliva and tear production which are the most salient symptoms of SS and is safe for consumption, it may provide a new approach to help ameliorate SS.
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