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大鼠的作用机制  

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

作　　者：黄帅金 万荣文 赵梁 邓竣 白雪 HUANG Shuaijin;WAN Rongwen;ZHAO Liang;DENG Jun;BAI Xue(Hunan Provincial Hospital of Integrated Traditional Chinese and Western Medicine,Changsha 410006,Hunan,China;The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University,Luzhou 646099,Sichuan,China)

机构地区：[1]湖南省中西医结合医院,湖南长沙410006 [2]西南医科大学附属中医院,四川泸州646099

出　　处：《湖南中医杂志》2025年第3期130-138,共9页Hunan Journal of Traditional Chinese Medicine

基　　金：湖南省自然科学基金项目(2023JJ40397);湖南省中医药研究院院级项目(202022)。

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(PaO_(2))及氧合指数[PaO_(2)/吸入氧气浓度(FiO_(2))];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,PaO_(2)及PaO_(2)/FiO_(2)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。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(PaO_(2))and oxygenation index(PaO_(2)/fraction of inhaled oxygen[FiO_(2)]);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 PaO_(2) and PaO_(2)/FiO_(2)(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 Ting

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 

分 类 号：R285.5[医药卫生—中药学] R259.6[医药卫生—中医学]