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  

Immunoregulatory effect of Dachengqi decoction on endotoxic ARDS in rats

作　　者：李玉梅[1] 卫洪昌[1] 汪东颖[1] 

机构地区：[1]上海中医药大学基础医学院病理教研室,上海201203

出　　处：《中国病理生理杂志》2009年第10期2027-2032,共6页Chinese Journal of Pathophysiology

基　　金：上海市教委高水平特色发展资助项目(No.2005-81)

摘　　要：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。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. coil 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.

关 键 词：大承气汤 脂多糖类 呼吸窘迫综合征 急性肺损伤 地塞米松 肿瘤坏死因子 

分 类 号：R361[医药卫生—病理学] R561[医药卫生—基础医学]