Rosiglitazone Improves Glucocorticoid Resistance in a Sudden Sensorineural Hearing Loss by Promoting MAP Kinase Phosphatase-1 Expression
Rosiglitazone Improves Glucocorticoid Resistance in a Sudden Sensorineural Hearing Loss by Promoting MAP Kinase Phosphatase-1 Expression
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罗格列酮通过促进 MAP 激酶磷酸酶 1 表达改善突发感音神经性听力损失中的糖皮质激素抵抗
DOI：
10.1155/2019/7915730
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发表时间：
2019-05
影响因子：
4.6
通讯作者：
杨光
中科院分区：
文献类型：
--
作者：
夏俍;杨光
在本研究中，我们利用脂多糖（LPS）诱导的突发性感音神经性听力损失（SSHL）豚鼠模型，分别研究MAP激酶磷酸酶-1 （MKP-1）和罗格列酮（RSG）在糖皮质激素抵抗和糖皮质激素敏感性中的作用。将猪分为对照组、LPS组、LPS+地塞米松组、LPS+RSG组和LPS+DEX+RSG组。通过听觉脑干反应测量来筛选他们的听力。免疫荧光染色法确定MKP-1在内耳的位置。western blotting检测MKP-1及相关蛋白在内耳组织中的表达水平。苏木精-伊红染色观察耳蜗形态变化。LPS组观察到严重的听力损失，而LPS+DEX+RSG组观察到听力损失的保护。MKP-1表达水平与保护听力损失呈正相关。RSG和DEX协同影响内耳炎症。综上所述，lps诱导的SSHL豚鼠模型对糖皮质激素的抗性可能是由于糖皮质激素诱导内耳组织中MKP-1功能受损，炎症抑制能力受损。我们的发现为开发治疗内耳炎症性疾病的潜在疗法提供了新的靶点。
In this study, we investigated the role of MAP kinase phosphatase-1 (MKP-1) and rosiglitazone (RSG) in glucocorticoid resistance and glucocorticoid sensitivity, respectively, using a guinea pig model of lipopolysaccharide- (LPS-) induced sudden sensorineural hearing loss (SSHL). The pigs were divided into control, LPS, LPS+dexamethasone (DEX), LPS+RSG, and LPS+DEX+RSG groups. Their hearing was screened by auditory brainstem response measurement. Immunofluorescence staining was used to identify the location of MKP-1 in the inner ear. The expression levels of MKP-1 and the related proteins in the inner ear were detected using western blotting. The morphological changes in the cochlea were observed via hematoxylin-eosin staining. Severe hearing loss was observed in the LPS group, as opposed to the protection from hearing loss observed in the LPS+DEX+RSG group. A positive correlation was observed between MKP-1 expression levels and protection from hearing loss. RSG and DEX synergistically influenced inner ear inflammation. In conclusion, resistance of LPS-induced SSHL guinea pig models to glucocorticoids may result from impaired MKP-1 function in inner ear tissues, induced by glucocorticoids, impairing the inhibition of inflammation. Our findings present novel targets to develop potential therapeutics to treat inflammatory diseases of the inner ear.
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影响因子：
4.6
作者：
Zhou QQ;Dai YH;Du XP;Hou J;Qi H;She WD
通讯作者：
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影响因子：
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