Platycodin D attenuates acute lung injury by suppressing apoptosis and inflammation in vivo and in vitro
Platycodin D attenuates acute lung injury by suppressing apoptosis and inflammation in vivo and in vitro
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DOI：
10.1016/j.intimp.2015.05.005
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发表时间：
2015-07-01
影响因子：
5.6
通讯作者：
Wang, Shumin
中科院分区：
文献类型：
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作者：
Tao, Weiwei;Su, Qiang;Wang, Shumin
桔梗皂苷D（Platycodin D，PLD）是桔梗（Platycodon grandiflorum（Jacq.）具有多种药理活性。本研究采用脂多糖（lipopolysaccharide，LPS）和博莱霉素（bleomycin，BLE）诱导的大鼠急性肺损伤（acute lung injury，ALI）模型，观察PLD对ALI的保护作用及其可能机制。将雌性BALB/c小鼠随机分为以下组：对照组、LPS组、LPS+地塞米松（2 mg/kg）组、LPS + PLD组LPS（50 mg/kg、100 mg/kg）组、LPS+地塞米松（2 mg/kg）组、LPS + PLO组（50 mg/kg、100 mg/kg）、BLE组、BLE+地塞米松（2 mg/kg）组、BLE + PLO组（50 mg/kg、100 mg/kg）、BLE+地塞米松（2 mg/kg）后处理组和BLE + PLO后处理组（50 mg/kg，100 mg/kg），PLO在LPS或BLE攻击小鼠之前或之后经口施用。处死小鼠，制备肺组织和支气管肺泡液（BALF）用于进一步分析。结果表明，PLO可显著降低肺湿干重比（W/D）、BALF中白细胞总数和中性粒细胞百分比，并呈剂量依赖性降低肺髓过氧化物酶（MPO）活性。此外，BALF中的细胞因子，包括白细胞介素（IL）-6，TNF-α也被发现显著抑制。PLO能有效抑制肺组织核因子-κ B（NF-κ B B）、Caspase-3和Bax的表达，恢复肺组织Bcl-2的表达，提高BALF中超氧化物歧化酶（SOD）活性。在存在和不存在PLO的情况下，用LPS刺激MLE-12细胞。PLD治疗组TNF-α、IL-6水平及NF-κ B、Caspase-3、Bax表达均显著下调，bcl-2表达显著上调，说明PLD治疗可改善MLE-12细胞的体内外ALI，其机制可能与抑制细胞凋亡和炎症反应有关。(C)2015爱思唯尔B. V.保留所有权利。
Platycodin D (PLD) is the major triterpene saponin in the root of Platycodon grandiflorum (Jacq.) with various pharmacological activities. The purpose of the present study was to evaluate the protective effects and possible mechanisms of PLD on acute lung injury (ALI) both in vivo and in vitro.In vivo, we used two ALI models, lipopolysaccharide (LPS)-induced ALI and bleomycin (BLE)-induced ALI to evaluate the protective effects and possible mechanisms of PLO. Female BALB/c mice were randomly divided into the following groups: control group, LPS group, LPS plus pre-treatment with dexamethasone (2 mg/kg) group, LPS plus pre-treatment with PLD groups (50 mg/kg, 100 mg/kg), LPS plus post-treatment with dexamethasone (2 mg/kg) group, LPS plus post-treatment with PLO groups (50 mg/kg, 100 mg/kg), BLE group, BLE plus pretreatment with dexamethasone (2 mg/kg) group, BLE plus pre-treatment with PLO groups (50 mg/kg, 100 mg/kg), BLE plus post-treatment with dexamethasone (2 mg/kg) group, and BLE plus post-treatment with PLO groups (50 mg/kg, 100 mg/kg), PLO was orally administered before or after LPS or BLE challenge with mice. Mice were sacrificed, and lung tissues and bronchoalveolar fluid (BALF) were prepared for further analysis. Our results showed that PLO significantly decreased lung wet-to-dry weight ratio (lung W/D weight ratio), total leukocyte number and neutrophil percentage in the BALF, and myeloperoxidase (MPO) activity of lung in a dose-dependent manner. Besides, cytokine levels, including interleukin (IL)-6, tumor neurosis factor (TNF)-alpha were also found significantly inhibited in BALF. Furthermore, PLO effectively inhibited the expressions of nuclear factor kappa B (NF-kappa B), Caspase-3 and Bax in the lung tissues, as well as restored the expression of Bcl-2 in the lungs and improved the superoxide dismutase (SOD) activity in BALF.In vitro, we used LPS-challenged cell model to evaluate the protective effects and possible mechanisms of PLO. MLE-12 cells were stimulated with LPS in the presence and absence of PLO. The levels of TNF-alpha, IL-6 and the expressions of NF-kappa B, Caspase-3, and Bax were remarkably down-regulated, while the expression of bcl-2 was significantly up-regulated in PLD treatment groups in MLE-12 cells.These results showed that the administration of PLD improved ALI both in vivo and in vitro, possibly through suppressing apoptosis and inflammation. (C) 2015 Elsevier B.V. All rights reserved.