Intranasal Application of Budesonide Attenuates Lipopolysaccharide-Induced Acute Lung Injury by Suppressing Nucleotide-Binding Oligomerization Domain-Like Receptor Family, Pyrin Domain-Containing 3 Inflammasome Activation in Mice
Intranasal Application of Budesonide Attenuates Lipopolysaccharide-Induced Acute Lung Injury by Suppressing Nucleotide-Binding Oligomerization Domain-Like Receptor Family, Pyrin Domain-Containing 3 Inflammasome Activation in Mice
复制标题
鼻内应用布地奈德通过抑制小鼠中核苷酸结合寡聚化结构域样受体家族、含 Pyrin 结构域的 3 炎症小体激活来减轻脂多糖诱导的急性肺损伤
DOI：
10.1155/2019/7264383
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发表时间：
2019-01-01
影响因子：
4.1
通讯作者：
Zhu, Zhao-Qiong
中科院分区：
文献类型：
--
作者：
Dong, Liang;Zhu, Yu-Hang;Zhu, Zhao-Qiong
目的探讨布地奈德对内毒素诱导的小鼠急性肺损伤(ALI)的保护作用及其机制。方法成年雄性C57BL/6小鼠随机分为3组：对照组、ALI组和ALI + 布地奈德组。气管内注射脂多糖(5 mg/kg)建立小鼠ALI模型。布地奈德组在注射 前1 h鼻内注射布地奈德(0.5 + mg/kg)。注射内毒素12h后处死小鼠。用苏木精-伊红染色和病理评分评价病理损伤。行支气管肺泡灌洗。计数支气管肺泡灌洗液(BALF)中细胞总数、中性粒细胞和巨噬细胞数。采用酶联免疫吸附试验检测肺泡灌洗液和血清中促炎症细胞因子肿瘤坏死因子-α、单核细胞趋化蛋白-1和白细胞介素1-β的表达。Western blotting检测核苷酸结合的寡聚结构域样受体家族--含吡咯结构域3(NLRP3)炎症体的表达。腹腔注射致死剂量的脂多糖(40 mg/kg)，观察布地奈德对小鼠存活率的影响。结果布地奈德可明显减轻ALI小鼠的病理损伤，降低病理评分。布地奈德能明显减少ALI小鼠BALF中细胞总数、中性粒细胞和巨噬细胞的数量。此外，布地奈德还能显著降低ALI小鼠肺泡灌洗液和血清中肿瘤坏死因子-α和单核细胞趋化蛋白-1的表达。布地奈德显著抑制肺组织中NLRP3和前Caspase-1的表达，降低肺泡灌洗液中IL-1β的含量，表明布地奈德抑制NLRP3炎性小体的激活。此外，我们发现布地奈德提高了ALI小鼠的存活率，ALI接受了致命剂量的内毒素。结论布地奈德抑制小鼠NLRP3炎性小体激活可减轻脂多糖诱导的ALI小鼠肺损伤。
Aim To investigate the protective effects of budesonide against lipopolysaccharide- (LPS-) induced acute lung injury (ALI) in a murine model and its underlying mechanism. Methods Adult male C57BL/6 mice were divided into three groups: control, ALI, and ALI + budesonide groups. LPS (5 mg/kg) was intratracheally injected to induce ALI in mice. Budesonide (0.5 mg/kg) was intranasally given 1 h before LPS administration in the ALI + budesonide group. Twelve hours after LPS administration, all mice were sacrificed. Hematoxylin-eosin staining and pathological scores were used to evaluate pathological injury. Bronchoalveolar lavage was performed. The numbers of total cells, neutrophils, and macrophages in the bronchoalveolar lavage fluid (BALF) were counted. Enzyme-linked immunosorbent assay was employed to detect the proinflammatory cytokines in BALF and serum, including tumor necrosis factor- (TNF-) α, monocyte chemoattractant protein- (MCP-) 1, and interleukin- (IL-) 1β. The expression of the nucleotide-binding oligomerization domain-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome was detected by western blotting. A lethal dose of LPS (40 mg/kg, intraperitoneally) was injected to evaluate the effects of budesonide on survival rates. Results Budesonide pretreatment dramatically attenuated pathological injury and reduced pathological scores in mice with ALI. Budesonide pretreatment obviously reduced the numbers of total cells, neutrophils, and macrophages in the BALF of mice with ALI. Additionally, budesonide dramatically reduced TNF-α and MCP-1 expression in the BALF and serum of mice with ALI. Budesonide significantly suppressed NLRP3 and pro-caspase-1 expression in the lung and reduced IL-1β content in the BALF, indicating that budesonide inhibited the activation of the NLRP3 inflammasome. Furthermore, we found that budesonide improved the survival rates of mice with ALI receiving a lethal dose of LPS. Conclusion Suppression of NLRP3 inflammasome activation in mice via budesonide attenuated lung injury induced by LPS in mice with ALI.