| 引用本文: |
张冉阳, 欧阳倪冰, 王鹏, 周芳亮, 高强.加减麦门冬汤对小鼠急性肺损伤及TLR4/MyD88/NF-κB p65信号通路的影响[J].湖南中医药大学学报,2025,45(5):795-802[点击复制] |
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| 加减麦门冬汤对小鼠急性肺损伤及TLR4/MyD88/NF-κB p65信号通路的影响 |
| 张冉阳,欧阳倪冰,王鹏,周芳亮,高强 |
| (湖南中医药大学, 湖南 长沙 410208) |
| 摘要: |
| 目的 探讨加减麦门冬汤（以下简称“麦门冬汤”）对脂多糖（LPS）诱导的急性肺损伤（ALI）的作用及机制。方法 42只BALB/c小鼠随机分为6组，每组7只，LPS诱导小鼠ALI造模，即对照组、模型组（5 mg/kg）、地塞米松组（5 mg/kg）、麦门冬汤低剂量组（7.5 g/kg）、麦门冬汤中剂量组（15 g/kg）、麦门冬汤高剂量组（30 g/kg）。采用肺湿干比（W/D）对小鼠肺水肿程度进行评价，HE染色观察小鼠肺组织病理变化；ELISA法检测小鼠血清炎症因子白细胞介素（IL）-1β、IL-6、肿瘤坏死因子-α（TNF-α）表达水平；比色法检测小鼠肺组织氧化应激相关指标丙二醛（MDA）、一氧化氮（NO）、总超氧化物歧化酶（T-SOD）表达水平；Western blot法检测肺组织Toll样受体4（TLR4）/髓系分化因子88（MyD88）/核转录因子-κB p65（NF-κB p65）通路TLR4、MYD88、NF-κB p65、p-NF-κB p65蛋白表达水平。结果 与对照组比较，模型组小鼠肺组织出血、水肿、炎细胞浸润程度相对加重，血清炎症因子IL-1β、IL-6、TNF-α表达水平显著升高（P＜0.01）；肺组织NO、MDA含量以及TLR4、MyD88、p-NF-κB p65/NF-κB p65蛋白表达水平显著升高（P＜0.01），T-SOD表达水平显著降低（P＜0.01）。与模型组比较，地塞米松组及麦门冬汤中、高剂量组小鼠肺组织出血、水肿、炎症细胞浸润程度相对减轻，血清炎症因子IL-1β、IL-6、TNF-α表达水平显著降低（P＜0.01）；肺组织NO、MDA含量以及TLR4、MyD88、p-NF-κB p65/NF-κB p65蛋白表达水平降低（P＜0.01或P＜0.05），T-SOD表达水平显著升高（P＜0.01）。与麦门冬汤低剂量组比较，麦门冬汤中、高剂量组小鼠肺组织出血、水肿、炎症细胞浸润程度相对减轻，麦门冬汤高剂量组血清炎症因子IL-1β、IL-6、TNF-α表达水平显著降低（P＜0.01）；麦门冬汤高剂量组肺组织NO、MDA表达水平及p-NF-κB p65/NF-κB p65蛋白表达水平显著降低（P＜0.01），T-SOD表达则显著升高（P＜0.01）。结论 麦门冬汤有较好的修复小鼠ALI的作用，其机制可能与干预TLR4/MyD88/NF-κB p65信号通路相关蛋白表达从而减轻炎症反应相关。 |
| 关键词: 急性肺损伤 加减麦门冬汤 脂多糖 炎症 TLR4/MyD88/NF-κB p65信号通路 |
| DOI：10.3969/j.issn.1674-070X.2025.05.003 |
| 投稿时间：2025-01-03 |
| 基金项目:国家自然科学基金项目（82104941）；中西医结合病原生物学湖南省重点实验室开放基金（2022KFJJ06）；湖南中医药大学2023年大学生创新创业训练计划（湘教通〔2023〕132号）第224号；湖南中医药大学中西医结合一流学科开放基金（2020ZXYJH03，2020ZXYJH73）；湖南中医药大学一流学科《基础医学》（NO:1）；湖南中医药大学重点培育学科基础医学学科（校行发规字〔2023〕2号）资助。 |
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| Effects of modified Maimendong Decoction on acute lung injury in mice and the TLR4/MyD88/NF-κB p65 signaling pathway |
| ZHANG Ranyang, OUYANG Nibing, WANG Peng, ZHOU Fangliang, GAO Qiang |
| (Hunan University of Chinese Medicine, Changsha, Hunan 410208, China) |
| Abstract: |
| Objective To investigate the effects and mechanisms of modified Maimendong Decoction (MMD) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. Methods Forty-two BALB/c mice were randomly divided into six groups with 7 mice in each group: control group, model group (LPS 5 mg/kg), dexamethasone group (5 mg/kg), and low- (7.5 g/kg), medium- (15 g/kg), and high-dose (30 g/kg) MMD groups. LPS was used to induce ALI in mice. The lung wet/dry (W/D) ratio was measured to assess pulmonary edema. HE staining was employed to observe histopathological changes in lung tissues. ELISA was used to detect serum levels of inflammatory cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α). Colorimetric assays were performed to evaluate oxidative stress-related indicators in lung tissues, such as expression levels of malondialdehyde (MDA), nitric oxide (NO), and total superoxide dismutase (T-SOD). Western blot was conducted to determine the protein expression levels of TLR4, MyD88), NF-κB p65, and p-NF-κB p65 in the Toll-like receptor 4 (TLR4)/ myeloid differentiation factor 88 (MyD88)/nuclear transcription factor-κB p65 (NF-κB p65) signaling pathway. Results Compared with the control group, the model group exhibited aggravated pulmonary hemorrhage, edema, and inflammatory cell infiltration. Serum levels of inflammatory cytokines IL-1β, IL-6, and TNF-α significantly elevated (P<0.01). Lung tissue levels of NO and MDA, as well as protein expression levels of TLR4, MyD88, and p-NF-κB p65/NF-κB p65 markedly increased (P<0.01), while T-SOD expression level decreased (P<0.01). In comparison to the model group, the dexamethasone group and the medium- and high-dose MMD groups showed relatively reduced pulmonary hemorrhage, edema, and inflammatory cell infiltration. Serum expression levels of IL-1β, IL-6, and TNF-α were significantly lower (P<0.01), and lung tissue levels of NO and MDA, along with TLR4, MyD88, and p-NF-κB p65/NF-κB p65 protein expression levels, decreased (P<0.01 or P<0.05), whereas T-SOD expression level elevated (P<0.01). Compared with the low-dose MMD group, the medium- and high-dose MMD groups demonstrated further attenuation of pulmonary hemorrhage, edema, and inflammation. The high-dose MMD group showed markedly reduced serum expression levels of IL-1β, IL-6, and TNF-α (P<0.01), as well as decreased lung tissue expression levels of NO, MDA, and p-NF-κB p65/NF-κB p65 proteins (P<0.01), accompanied by increased T-SOD expression levels (P<0.01). Conclusion MMD exhibits protective effects against ALI in mice, likely through modulating the TLR4/MyD88/NF-κB p65 signaling pathway to attenuate inflammatory responses. |
| Key words: acute lung injury modified Maimendong Decoction (MMD) lipopolysaccharide inflammation TLR4/MyD88/NF-κB p65 signaling pathway |
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