大承气汤治疗大鼠内毒素性ARDS的疗效分析及免疫调节机制研究

目的： 探讨大承气汤对内毒素“二次打击”致急性呼吸窘迫综合征（ARDS）的防治作用，为中西医结合防治呼吸道疾病提供有效依据。方法: 48只健康雄性Wistar大鼠随机分为4组:生理盐水对照组、ARDS模型组、大承气汤治疗组、地塞米松治疗组，每组12只。采用大肠杆菌脂多糖(LPS) “二次打击”建立大鼠ARDS动物模型，结合动脉血气分析、肺湿/干重(W／D)比值及肺组织病理学观察和评分，评价大承气汤的药理作用；酶联免疫吸附法（ELISA）测定血浆与支气管肺泡灌洗液（BALF）中肿瘤坏死因子-α（TNF-α）、白细胞介素-1（IL-1）、IL-10水平，探讨大承气汤的药理作用和免疫调节机制。结果: (1)大承气汤可以显著提高ARDS大鼠动脉血氧分压，增加血氧饱和度，降低肺湿/干重比值和肺病理损伤，减轻肺水肿和肺部炎症反应，因而具有改善肺通气、抑制肺部炎症反应、减轻肺损伤功能。(2)大承气汤可使血浆促炎细胞因子（TNF-α、IL-1）和抗炎细胞因子（IL-10）水平同时降低，使BALF中TNF-α、IL-1水平降低同时IL-10水平却升高，因而表现出对全身炎症反应和局部炎症反应不同的免疫调节机能。结论: 大承气汤抑制肺部炎症反应除与下调全身炎症反应水平有关，同时还与促进肺部抗炎介质产生、调节肺部促炎介质/抗炎介质的平衡有关。

Immunoregulatory effect of Dachengqi decoction on endotoxic ARDS in rats

AIM: To investigate the effect of Dachengqi decoction (DD) on the acute respiratory distress syndrome (ARDS) in rat model induced by endotoxin “two-hit”. METHODS: 48 healthy male Wistar rats were randomly divided into 4 groups: control group, ARDS model group, ARDS+DD treatment group and ARDS+dexamethasone treatment group (12 in each group). E. coli lipopolysaccharide (LPS) “two-hit” induced ARDS model in rats was established. The arterial blood gas analysis, lung wet/dry weight (W/D) ratio and lung tissue pathology observation and scoring were measured to evaluate the pharmacological effects of DD on ARDS. The levels of TNF-α, IL-1 and IL-10 were determined by ELISA to explore the immune regulatory mechanism of DD. RESULTS: (1) Treatment with DD significantly improved blood pressure in rats, increased oxygen saturation, decreased lung wet/dry weight ratio and lung injury score, relieved pulmonary edema and the inflammatory responses. (2) DD suppressed the productions of systemic and pulmonary pro-inflammatory mediators and promoted the release of anti-inflammatory mediators in lung. CONCLUSION: The inhibitory effects of DD treatment on pulmonary inflammatory response are not only related to reducing the extent of systemic inflammatory response, but also promote pulmonary anti-inflammatory production and regulate the balance of pulmonary pro-inflammatory mediators and anti-inflammatory cytokines. This specific regulatory effect protects the target organ from excessive inflammatory organ injury, discloses that DD has advantages in the treatment of endotoxic ARDS.