Licochalcone A Protects the Blood-Milk Barrier Integrity and Relieves the Inflammatory Response in LPS-Induced Mastitis
Licochalcone A Protects the Blood-Milk Barrier Integrity and Relieves the Inflammatory Response in LPS-Induced Mastitis
复制标题
甘草查耳酮 A 保护血乳屏障完整性并缓解 LPS 引起的乳腺炎的炎症反应
DOI：
10.3389/fimmu.2019.00287
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发表时间：
2019-02-25
影响因子：
7.3
通讯作者：
Liu, Juxiong
中科院分区：
文献类型：
--
作者：
Guo, Wenjin;Liu, Bingrun;Liu, Juxiong
背景/目的：乳腺炎是一种急性临床炎症反应。乳腺炎的发生发展严重困扰着妇女的身心健康。甘草查尔酮A是甘草中的一种酚类化合物，具有抗炎作用。在此，我们研究了甘草查尔酮A对LPS诱导的小鼠乳腺炎的血乳屏障和炎症反应的影响。研究方法：在体内实验中，我们首先通过乳腺导管内注射LPS建立小鼠乳腺炎模型，然后检测甘草查尔酮A对该模型病理指标、炎症反应及血乳屏障的影响。在体内，在LPS孵育前用甘草查尔酮A处理小鼠乳腺上皮细胞（mMEC），观察其炎症反应和作为血乳屏障基本结构的紧密连接。最后，通过体内外实验研究丝裂原活化蛋白激酶（mitogen-activated protein kinase，MAPK）和AKT/NF-κB信号通路的激活，阐明了其抗炎作用机制。测试结果：体内实验结果表明甘草查尔酮A能显著减轻组织病理学损伤和炎症反应，改善血乳屏障的完整性。体外结果表明甘草查尔酮A抑制LPS诱导的炎症反应，并增加mMEC中ZO-1、occludin和claudin 3的蛋白水平。体内外机制研究发现甘草查尔酮A对LPS诱导的小鼠乳腺炎的抗炎作用通过MAPK和AKT/NF-κB信号通路介导。结论和影响：我们的实验共同表明甘草查尔酮A通过改善血乳屏障的完整性来保护LPS诱导的小鼠乳腺炎，并通过MAPK和AKT/NF-κB信号通路抑制炎症反应。
Background/Aims: Mastitis is an acute clinical inflammatory response. The occurrence and development of mastitis seriously disturb women's physical and mental health. Licochalcone A, a phenolic compound in Glycyrrhiza uralensis, has anti-inflammatory properties. Here, we examined the effect of licochalcone A on blood-milk barrier and inflammatory response in LPS-induced mice mastitis. Methods: In vivo, we firstly established mice models of mastitis by canal injection of LPS to mammary gland, and then detected the effect of licochalcone A on pathological indexes, inflammatory responses and blood-milk barrier in this model. In vivo, Mouse mammary epithelial cells (mMECs) were treated with licochalcone A prior to the incubation of LPS, and then the inflammatory responses, tight junction which is the basic structure of blood-milk barrier were analyzed. Last, we elucidated the anti-inflammatory mechanism by examining the activation of mitogen-activated protein kinase (MAPK) and AKT/NF-κB signaling pathways in vivo and in vitro. Result: The in vivo results showed that licochalcone A significantly decreased the histopathological impairment and the inflammatory responses, and improved integrity of blood-milk barrier. The in vitro results demonstrated that licochalcone A inhibited LPS-induced inflammatory responses and increase the protein levels of ZO-1, occludin, and claudin3 in mMECs. The in vivo and in vitro mechanistic study found that the anti-inflammatory effect of licochalcone A in LPS-induced mice mastitis was mediated by MAPK and AKT/NF-κB signaling pathways. Conclusions and Implications: Our experiments collectively indicate that licochalcone A protected against LPS-induced mice mastitis via improving the blood–milk barrier integrity and inhibits the inflammatory response by MAPK and AKT/NF-κB signaling pathways.