| 摘要: |
| 目的：基于肺血管通透性增高机制探究“肺肠同治法”治疗急性呼吸窘迫综合征（ARDS）大鼠的作用机制。方法：将60只SPF级SD雄性大鼠分为正常组、模型组、低剂量组、中剂量组和高剂量组，除正常组外，其余各组均采用油酸和内毒素刺激大鼠构建ARDS大鼠模型。造模成功后，低剂量组、中剂量组和高剂量组分别给予不同剂量［5 g/（kg·d）、10 g（kg·d）和20 g/（kg·d）］的复方葶苈子汤与大承气汤（以1∶1剂量配比）灌胃治疗。HE染色检测肺脏组织的病理变化并进行肺损伤评分;测定肺脏组织的湿干比重（W/D）;BCA蛋白检测试剂盒检测大鼠支气管肺泡灌洗液（BALF）的总蛋白浓度;采用血气分析仪测定大鼠的动脉氧分压（PaO2）及氧合指数［PaO2/吸入氧气浓度（FiO2）］;ELISA法检测大鼠血清中涎液化糖链抗原（KL6）、晚期糖基化终末产物受体（RAGE）和血管紧张素2（Ang-2）的水平;流式细胞术检测辅助型T细胞（Th17）和调节性T细胞（Treg）的百分比;伊文思蓝实验评估肺血管通透性。结果：与模型组相比，低、中、高剂量组大鼠肺组织病理损伤和肺损伤评分均有所改善，W/D值和BALF的总蛋白水平显著降低，PaO2及PaO2/FiO2明显升高（P<0.01，P<0.05）;大鼠血清中KL6、RAGE和Ang-2水平显著降低（P<0.01，P<0.001）;Th17细胞的百分比、肺血管通透性显著降低，而Treg细胞的百分比明显升高（P<0.01）。结论：根据“肺肠同治法”治疗原则配制的复方葶苈子汤和大承气汤联合应用，可改善ARDS大鼠的症状，其机制可能是通过减轻炎症因子水平、维持Th17/Treg平衡及降低肺血管通透性来实现。 |
| 关键词: 急性呼吸窘迫综合征 肺肠同治法 复方葶苈子汤 大承气汤 肺血管通透性 炎症因子 免疫微环境 |
| DOI： |
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| Mechanism of action of simultaneous treatment of lung and intestine in rats with acute respiratory distress syndrome：A study based on the mechanism of increase in pulmonary vascular permeability |
| HUANG Shuaijin,WAN Rongwen,ZHAO Liang |
| (Hunan Provincial Hospital of Integrated Traditional Chinese and Western Medicine，Changsha 410006，Hunan，China) |
| Abstract: |
| Objective：To investigate the mechanism of action of simultaneous treatment of lung and intestine in rats with acute respiratory distress syndrome (ARDS) based on the mechanism of increase in pulmonary vascular permeability.Methods：A total of 60 male specific pathogen-free Sprague-Dawley rats were divided into normal group，model group，low-dose group，middle-dose group，and high-dose group，and all rats except those in the normal group were stimulated with oleic acid and endotoxin to establish a rat model of ARDS.After successful modeling，the rats in the low-，middle-，and high-dose groups were given compound Tinglizi decoction (at a dose of 5，10，and 20 g/（kg·d，respectively) and Dachengqi decoction (at a dose proportion of 1∶1) by gavage.HE staining was used to observe the pathological changes of lung tissue and determine lung injury score;wet-to-dry lung weight ratio (W/D) was measured;BCA protein detection kit was used to measure the concentration of total protein in bronchoalveolar lavage fluid (BALF);a blood-gas analyzer was used to measure arterial partial pressure of oxygen (PaO2) and oxygenation index (PaO2/fraction of inhaled oxygen ［FiO2］);ELISA was used to measure the serum levels of Krebs Von den Lungen-6 (KL6)，receptor for advanced glycation end products (RAGE)，and angiotensin-2 (Ang-2);flow cytometry was used to measure the percentage of Th17 cells and Treg cells;the Evans blue experiment was used to evaluate pulmonary vascular permeability.Results：Compared with the model group，the low-，middle-，and high-dose groups had certain improvements in pathological lung injury and lung injury score，with significant reductions in W/D ratio and total protein in BALF and significant increases in PaO2 and PaO2/FiO2 (P<0.01 or P<0.05).There were significant reductions in the serum levels of KL6，RAGE，and Ang-2 (P<0.01 or P<0.001)，as well as significant reductions in the percentage of Th17 cells and pulmonary vascular permeability and a significant increase in the percentage of Treg cells (P<0.01).Conclusion：Compound Tinglizi decoction combined with Dachengqi decoction based on the principle of “simultaneous treatment of lung and intestine” can improve the symptoms of rats with ARDS，possibly by alleviating the levels of inflammatory factors，maintaining Th17/Treg balance，and reducing pulmonary vascular permeability. |
| Key words: acute respiratory distress syndrome simultaneous treatment of lung and intestine compound Tinglizi decoction Dachengqi decoction pulmonary vascular permeability inflammatory factors immune microenvironment |
