Xiang Yijin, Cai Min, Li Xiangting, Bao Xuxia, Cai Dingfang
Department of Integrative Medicine, Zhongshan Hospital, Fudan University, Institutes of Integrative Medicine, Fudan University, Development Project of Shanghai Peak Disciplines-Integrative Medicine, Shanghai 200032, China.
Evid Based Complement Alternat Med. 2021 Sep 27;2021:8257495. doi: 10.1155/2021/8257495. eCollection 2021.
As a traditional Chinese medicine prescription, Xiao-Xu-Ming decoction (XXMD) could reduce the incidence of lung infection of patients with cerebral infarction. Nonetheless, the therapeutic mechanisms of XXMD in acute lung injury (ALI) remain to be elucidated. Our study was aimed to assess the effects of XXMD protects against ALI.
ALI model was induced by intraperitoneal injection of lipopolysaccharide (LPS) . , human pulmonary alveolar epithelial cells (HPAEpiC) were treated with XXMD and were followed by LPS treatment. The levels of ZO-1, CLDN4, NLRP3, and caspase 1 were detected by Western blot, and the content of IL-1 and IL-18 was determined by ELISA. Transepithelial electrical resistance was used to detect the cell permeability. The reactive oxygen species (ROS) levels within the cells were evaluated by flow cytometry.
Our results showed that XXMD attenuated LPS-induced oxidative stress, barrier dysfunction, and the activation of NLRP3 inflammasome , as evidenced by enhanced ROS production, TEER levels, expression of NLRP3 and caspase 1 (p20) and release of IL-1 and IL-18, and weakened cell permeability. In addition, XXMD could counteract the effects of NLRP3 overexpression on HPAEpiC and vice versa. XXMD treatment also ameliorated the degree of neutrophil infiltration, barrier dysfunction, and the activation of NLRP3 in LPS-induced ALI lung tissues .
The findings showed that XXMD could alleviate LPS-induced ALI injury and inhibit inflammation and suppress ROS/NLRP3 signaling pathway, which were involved in these protective effects.
作为一种中药方剂,小续命汤(XXMD)可降低脑梗死患者肺部感染的发生率。然而,XXMD在急性肺损伤(ALI)中的治疗机制仍有待阐明。我们的研究旨在评估XXMD对ALI的保护作用。
通过腹腔注射脂多糖(LPS)诱导ALI模型。用XXMD处理人肺泡上皮细胞(HPAEpiC),然后进行LPS处理。通过蛋白质免疫印迹法检测紧密连接蛋白1(ZO-1)、闭合蛋白4(CLDN4)、NLR家族含pyrin结构域蛋白3(NLRP3)和半胱天冬酶1的水平,并用酶联免疫吸附测定法测定白细胞介素-1(IL-1)和白细胞介素-18的含量。采用跨上皮电阻检测细胞通透性。通过流式细胞术评估细胞内活性氧(ROS)水平。
我们的结果表明,XXMD减轻了LPS诱导的氧化应激、屏障功能障碍和NLRP3炎性小体的激活,这表现为ROS生成增加、跨上皮电阻水平、NLRP3和半胱天冬酶1(p20)表达以及IL-1和IL-18释放增加,以及细胞通透性减弱。此外,XXMD可以抵消NLRP3过表达对HPAEpiC的影响,反之亦然。XXMD治疗还改善了LPS诱导的ALI肺组织中中性粒细胞浸润程度、屏障功能障碍和NLRP3的激活。
研究结果表明,XXMD可以减轻LPS诱导的ALI损伤,抑制炎症并抑制ROS/NLRP3信号通路,这些都参与了这些保护作用。