| 李妙晨,卞相丽,郑 芳,蒋 芹,吴志敏.基于TGF-β1-Smad2信号通路探讨布地奈德对高氧诱导支气管肺发育不良新生小鼠的保护作用及机制研究[J].,2021,(20):3823-3827 |
| 基于TGF-β1-Smad2信号通路探讨布地奈德对高氧诱导支气管肺发育不良新生小鼠的保护作用及机制研究 |
| To Investigate the Protective Effect and Mechanism Study of Budesonide on Hyperoxia-induced Bronchopulmonary Dysplasia in Neonatal Mice Based on TGF-β1-Smad2 Signaling Pathway |
| 投稿时间：2021-04-10 修订日期：2021-04-30 |
| DOI：10.13241/j.cnki.pmb.2021.20.005 |
| 中文关键词: 支气管肺发育不良 布地奈德 炎症反应 TGF-β1 Smad2 NLRP3 Caspase-1 |
| 英文关键词: Bronchopulmonary dysplasia Budesonide Inflammatory response TGF-β1 Smad2 NLRP3 Caspase-1 |
| 基金项目:上海市卫生健康委先进适宜技术推广项目(2019SY051)；上海市浦东新区卫生和计划生育委员会卫生计生科研项目(PW2017D-7)；上海市第六人民医院东院院级科研基金项目(院人才2016021) |
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| 中文摘要: |
| 摘要 目的：基于转化生长因子-β1(TGF-β1)-母亲DPP同源物2(Smad2)信号通路探讨布地奈德对高氧诱导支气管肺发育不良(BPD)新生小鼠的保护作用及机制研究。方法：将60只SD小鼠随机分为对照组、模型组以及布地奈德低/中/高等剂量组，每组12只。对照组暴露于空气中，模型组和布地奈德低、中、高剂量组暴露于高氧环境中，建立BPD模型。布地奈德低/中/高等剂量组建模24 h后每日雾化吸入1 mL/2 mL/4 mL布地奈德混悬液，12 h/次，持续雾化至处死，对照组和模型组建模24 h后每日雾化吸入生理盐水，12 h/次。建模7 d、14 d，HE染色观察各组肺组织形态学变化，Image-Pro Plus 6.0 软件测定放射状肺泡计数(RAC)、肺泡平均截距(MLI)，免疫印迹法检测肺组织TGF-β1、Smad2、核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)、半胱氨酸天冬氨酸蛋白酶-1(Caspase-1)蛋白水平，酶联免疫吸附法检测血清白介素(IL)-1β、IL-18水平。结果：建模7 d、14 d后，模型组肺组织结构破坏严重，肺泡结构简单，体积增大，形成肺大疱，组织变形随着建模时间延长而加重。布地奈德低、中、高剂量组肺组织结构破坏程度随着布地奈德浓度增加而好转，肺泡结构逐渐完整。与对照组比较，模型组建模7 d、14 d后RAC明显降低，MLI和肺组织TGF-β1、Smad2、NLRP3、Caspase-1蛋白水平及血清IL-1β、IL-18水平明显升高(P＜0.05)。与模型组比较，布地奈德低、中、高剂量组建模7 d、14 d后RAC逐渐增加，MLI和肺组织TGF-β1、Smad2、NLRP3、Caspase-1蛋白水平及血清IL-1β、IL-18水平逐渐降低(P＜0.05)。结论：布地奈德可能通过调控NLRP3/Caspase-1信号通路抑制炎症反应，调控TGF-β1/Smad2信号通路抑制肺纤维化进程，在BPD新生小鼠中发挥保护作用。 |
| 英文摘要: |
| ABSTRACT Objective: To investigate the protective effect and mechanism study of budesonide on hyperoxia-induced bronchopulmonary dysplasia (BPD) in neonatal mice based on transforming growth factor-β1(TGF-β1)-mothers against decapentaplegic homolog 2 (Smad2) signaling pathway. Methods: 60 SD mice were randomly divided into control group, model group, low/middle/high dose budesonide groups, with 12 mice in each group. The control group was exposed to the air, and the model group and low, medium, and high dose budesonide groups were exposed to a high oxygen environment to establish a BPD model. 24 h after modeling, the low/medium/high dose budesonide groups was inhaled with 1 mL/2 mL/4 mL budesonide suspension daily, 12 h/times, and continued to atomize until death, 24 h after modeling, the control group and the model group were atomized and inhaled normal saline daily, 12 h/times. 7 d and 14 d after modeling, HE staining was used to observe the morphological changes of lung tissue in each group. Radial alveolar count (RAC) and mean alveolar intercept(MLI) were measured by Image-Pro Plus 6.0 software, and TGF-β1, Smad2, nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3) and cysteine aspartate protease-1(caspase-1) protein levels were detected by Western blotting. Serum interleukin (IL)-1β and IL-18 levels were detected by enzyme-linked immunosorbent assay. Results: 7 d and 14 d after modeling, the lung tissue structure of the model group was severely damaged, the alveolar structure was simple, the volume increased, and bullae were formed, and the tissue deformation increased with the extension of modeling time. The degree of lung tissue damage in low, medium and high dose budesonide groups improved with the increase of budesonide concentration, and the alveolar structure was gradually complete. Compared with the control group, the RAC of the model group was significantly reduced at 7 d and 14 d after modeling, and the MLI and lung tissue TGF-β1, Smad2, NLRP3, Caspase-1 protein levels and serum IL-1β, IL-18 levels were significantly increased (P＜0.05). Compared with the model group, the RAC of the low, medium and high dose budesonide groups gradually increased, MLI and lung tissue TGF-β1, Smad2, NLRP3, Caspase-1 protein levels, and serum IL-1β, IL-6 levels gradually decreased (P＜0.05). Conclusion: Budesonide may inhibit inflammatory response by regulating the NLRP3/Caspase-1 signaling pathway, and regulate the TGF-β1/Smad2 signaling pathway to inhibit the process of pulmonary fibrosis, and play a protective role in BPD in neonatal mice. |
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