中药四磨汤在急性呼吸窘迫综合征中的作用研究

A study on effect of traditional Chinese medicine Simo decoction on acute respiratory distress syndrome

目的 观察四磨汤口服液对急性呼吸窘迫综合征（ARDS）小鼠血清和支气管肺泡灌洗液（BALF）中炎症因子的影响,并探讨其作用机制.方法 将50只BALB/c小鼠按随机数字表法分为正常对照组、ARDS模型组和小、中、大剂量四磨汤口服液组,每组10只.采用气管内滴入脂多糖（LPS）的方法复制ARDS模型,正常对照组给予等量生理盐水.小、中、大剂量四磨汤口服液组分别于制模成功后立即给予四磨汤口服液,按7.56 mL＆#183;kg-1＆#183;d-1等效剂量的1、2、4倍灌胃,正常对照和ARDS模型组制模后不进行干预.给药后24 h处死动物,取肺组织观察病理学改变;取血清和BALF检测肿瘤坏死因子-α（TNF-α）、白细胞介素（IL-1β和IL-6）水平;同时检测血清超氧化物歧化酶（SOD）的含量.结果 肺组织病理学观察显示,正常对照组无明显炎症渗出;ARDS模型组肺组织炎症渗出明显,血清和BALF中TNF-α（ng/L：1759±303比104±27,2506±674比507±46）、IL-1β（ng/L：209±16比114±11,7325±826比3513±498）和IL-6（ng/L：144±38比47±7,126±38比15±7）水平明显增加,血清SOD含量（kU/L：40.26±2.54比50.68±3.75）明显降低（均P＜0.05）,说明制模成功.与ARDS模型组比较,小、中、大剂量四磨汤口服液呈剂量依赖性抑制肺组织炎症渗出程度,以及血清、BALF中TNF-α、IL-1β和IL-6水平,增加血清SOD含量〔血清：TNF-α（ng/L）为1642±276、1126±154、817±102比1759±303,IL-1β（ng/L）为198±12、170±11、141±13比209±16,IL-6（ng/L）为127±22、82±16、41±15比144±38,SOD（kU/L）为42.11±1.64、45.18±1.15、48.09±1.23比40.26±2.54;BALF：TNF-α（ng/L）为2479±446、1632±330、1067±223比2506±674,IL-1β（ng/L）为6939±725、5398±625、4401±210比7325±826,IL-6（ng/L）为106±30、68±13、34±10比126±38,均P＜0.05〕,且以高剂量组的变化更显著.结论 四磨汤口服液可以抑制ARDS的炎症反应,降低氧化应激、减少ARDS小鼠肺损伤.

Objective To investigate the effect of Simo decoction oral liquid on inflammatory in acute respiratory distress syndrome （ARDS） mouse serum and the bronchoalveolar lavage fluid （BALF） and to explore the mechanism.Methods Fifty BALB/c mice were divided into normal control group, ARDS model group, small, moderate and large dose Simo decoction oral liquid-treated groups （simplified as Simo groups） according to random number table method （n=10, in each group）. The ARDS model mice were replicated by lipopolysaccharide （LPS） tracheal instillation, and the mice in normal control group were given the same amount of normal saline. Immediately after the success of modeling, the mice were gavaged with 1, 2, 4 times the equivalent dose Simo decoction oral liquid of 7.56 mL＆#183;kg-1＆#183;d-1 in small, moderate or large dose Simo groups respectively, and there was no intervention in the normal control group or ARDS model group. All the mice were sacrificed at 24 hours after the respective drug amount or normal saline was given in various groups. The lung samples were taken for histologic evaluation, and BALF and serum samples were analyzed for the tumor necrosis factor-α（TNF-α）, interleukin （IL-1β, IL-6）, and in the mean time the level of serum superoxide dismutase （SOD） was detected.Results The pathological observation of lung tissue showed： there was no obvious inflammatory exudation in lung tissue of mice in normal control group; the inflammatory exudation in lung tissue of mice was increased significantly, the level of TNF-α （ng/L： 1759±303 vs. 104±27, 2506±674 vs. 507±46）, IL-1β（ng/L： 209±16 vs. 114±11, 7325±826 vs. 3513±498） and IL-6 （ng/L： 144±38 vs. 47±7, 126±38 vs. 15±7） in serum and BALF were significantly increased, and the content of SOD （kU/L： 40.26±2.54 vs. 50.68±3.75） in serum was significantly decreased in ARDS model group （allP 〈 0.05）, indicating that animal model of ARDS was set up successfully. Compared with ARDS model group, in small, moderate and large dose Simo groups, the inflammation exudation in lung tissue of mouse was reduced, the levels of TNF-α, IL-1βand IL-6 in serum and BALF were reduced, and the content of SOD in serum was increased [serum： TNF-α（ng/L） was 1642±276, 1126±154, 817±102 vs. 1759±303, IL-1β（ng/L）was 198±12, 170±11, 141±13 vs. 209±16, IL-6 （ng/L） was 127±22, 82±16, 41±15 vs. 144±38, SOD （kU/L） was 42.11±1.64, 48.09±1.23 vs. 40.26±2.54; BALF： TNF-α（ng/L） was 2479±446, 1632±330, 1067±223 vs. 2506±674, IL-1β（ng/L）： 6939±725, 5398±625, 4401±210 vs. 7325±826, IL-6 （ng/L）： 106±30, 68±13, 34±10 vs. 126±38, allP 〈 0.05], showing the Simo decoction inhibiting the lung inflammation and the above levels of indexes inserum and BALF was in a dose-dependent manner, and the changes in large dose Simo group was the most significant 45.18±1.15, .Conclusions Simo decoction oral liquid can inhibit the inflammatory response of ARDS, reduce the oxidative stress and decrease the lung injury of mice with ARDS.