瑞芬太尼对兔内毒素性急性肺损伤时TNF-α及IL-8的影响  

Effects of remifentanil on TNF -α and IL - 8 on lipopolysaccharide - induced acute lung injury in rabbits

作　　者：周本昊[1] 杜成[1] 景亮[2] 刘晓甦[3] 

机构地区：[1]南京市胸科医院ICU,江苏南京210029 [2]东南大学附属中大医院麻醉科,江苏南京210009 [3]南京市胸科医院麻醉科,江苏南京210029

出　　处：《中国急救医学》2012年第8期696-700,I0001,共6页Chinese Journal of Critical Care Medicine

摘　　要：目的探讨瑞芬太尼对兔内毒素性急性肺损伤（ALI）时TNF-α及IL-8的影响。方法健康成年雄性新西兰大白兔30只，体质量2．5-3．5kg，随机分为5组（n=6）：对照组（C组）、内毒素组（ALI组）、低剂量瑞芬太尼组（LR组）、中剂量瑞芬太尼组（MR组）和高剂量瑞芬太尼组（HR组）。C组用生理盐水10mL静脉持续泵注30min；ALI组用大肠杆菌内毒素（LPS）0．5mg／kg静脉持续泵注30min；LR组、MR组和HR组分别静脉输注瑞芬太尼0．2、0．4和0．8μg／（kg·min）至处死，输注15min时开始给予LPS，方法同AU组。于LPS输注前即刻（11D）、输注结束后1、2．5、5．5h时记录平均动脉血压（MAP）、心率（HR）和气道峰压（Ppeak），测定动脉血氧分压（PaO2）和肿瘤坏死因子（TNF）-α、白细胞介素-8（IL-8）的活性，称量肺组织湿质量（w）和干质量（D），计算W／D，并在光镜和电镜下观察肺组织病理学结果。结果与c组比较，ALI组MAP、HR和Pa02降低，W／D、Ppeak和血浆TNF-α、IL-8含量明显升高（P〈0．05）；与ALI组比较，LR组、MR组和HR组MAP、HR升高，肺组织W／D降低，Ppeak和血浆TNF-α、IL-8含量降低，PaO2升高（P〈0．05）；与LR组比较，MR组和HR组MAP、HR、Ppeak、血清TNF-α、IL-8含量和肺组织W／D比降低，PaO2升高（P〈0．05）；与MR组比较，HR组肺组织W／D比降低，PaO2升高（P〈0．05）。LR组、MR组和HR组肺组织病理学损伤较ALI组减轻。结论瑞芬太尼可减轻兔内毒素性ALI，且呈剂量依赖性，其机制可能是通过抑制TNF-αd、IL-8的表达，进而抑制促炎症因子参与的“级联瀑布效应”，减轻肺损伤的程度。Objective To investigate the effects of remifentanil on TNF - αand IL - 8 on lipopolysaccharide- induced acute lung injury in rabbits. Methods Thirty healthy male New Zealand white rabbits weighing 2.5- 3.5 kg were randomly divided into 5 groups （ n = 6 each） ： group Ⅰ control （ group C） ; group Ⅱ ALl; group Ⅲ,Ⅳ, Ⅴ low, median and high dose RF ＋ LPS （ group LR, MR, HR）. The animals were anesthetized with intravenous 3% pentobarbital sodium 30 mg/kg, tracheostomized and mechanically ventilated. The carotid artery and j gular vein were cannulated for MAP and HR monitoring, blood sampling, and fluid and dr g administration. LPS 0.5 mg/kg in 10 ml of normal saline（ NS）was infused over 30 min in group Ⅱ- Ⅴ. Remifentanil 0.2, 0.4 or 0.8 μg/（ kg- rain） was infused 15 rain before LPS administration until the death of the animals. MAP, HR, peak airway pressure （Ppeak） , Pat2 and tumor necrosis factor （ TNF - α） , interleukin - 8 （ IL - 8 ） concentration were measured immediately before LPS infusion （ TO, baseline） and at 1,2.5 and 5.5 h after the end of LPS infusion. The animals were killed and the lungs were immediately removed for microscopic examination and determination of W/D lung weight ratio. Results MAP, HR and Pat2were significantly decreased while W/D ratio and Ppeak were significantly increased after iv LPS infusion as compared with control group. LPS significantly increased plasma TNF - α and IL - 8 concentration and damaged the structure of lung tissue. Remifentanil infusion significantly attenuated the LPS - induced changes in a dose - dependent manner. Conclusion Remifentanil reduces LPS - induced acute lung injury in rabbits which is dose - dependent. The possible mechanism of protective effect is that by inhibiting the expression of TNF - α, IL - 8, remifentanil can inhibit neutrophilic granulocyte aggregation in lung, interfere with the cascade effect of inflammatory factor, and relieve the impairment of lung.

关 键 词：瑞芬太尼 急性肺损伤(ALI) 内毒素血症 炎症因子 

分 类 号：R285.5[医药卫生—中药学]