乌司他丁对黑火药烟雾所致吸入性肺损伤大鼠的保护作用以及对IL-1β、TNF-α基因表达的抑制作用  

Protective effect of ulinastatin on inhalation lung injury caused by black gunpowder smoke in rats and its inhibitory effect on the mRNA expression of IL-1β and TNF-α

作　　者：刘一凡[1] 王正冠 唐红卫[1] 吴小利[2] 谢尹晶[2] 张洪瑞[2] 李登清[3] 王成彬[1] 

机构地区：[1]北京解放军总医院临床检验科,100853 [2]浙江温州温州医科大学检验医学与生命科学学院,325035 [3]长沙中南大学湘雅医学院医学检验系,410013

出　　处：《解放军医学杂志》2014年第3期235-239,共5页Medical Journal of Chinese People's Liberation Army

基　　金：全军“十二五”医学科研面上项目(CWS12J021)~~

摘　　要：目的探讨乌司他丁(UTI)对黑火药烟雾所致大鼠吸入性肺损伤的保护作用及其对白细胞介素1β(IL-1β)、肿瘤坏死因子α(TNF-α)mRNA表达的抑制作用。方法健康成年雄性Wistar大鼠30只,随机分为正常对照组(C组)、吸入性肺损伤组(I组)、乌司他丁高剂量组(UH组)、乌司他丁中剂量组(UM组)、乌司他丁低剂量组(UL组),每组6只。使用自制发烟装置建立大鼠吸入性肺损伤模型,UH组、UM组、UL组分别按100 000、50 000、20 000U/(kg.d)剂量给予UTI。处理40h后检测各组大鼠动脉血气、肺湿/干重比(W/D)、支气管肺泡灌洗液(BALF)中白细胞计数和蛋白含量、血清和肺组织髓过氧化物酶(MPO)活性、肺组织丙二醛(MDA)含量,并观察肺组织的大体及病理学改变。采用反转录荧光定量PCR检测肺组织Toll样受体4(TLR-4)、IL-1β、TNF-αmRNA的表达。结果 UH、UM、UL组的PaO2高于I组(P<0.05),W/D、BALF中白细胞计数低于I组(P<0.05),UM、UL组IL-1β和BALF中蛋白含量低于I组(P<0.05),3组PaO2、PaCO2、W/D、BALF中蛋白含量与C组比较差异均无统计学意义(P>0.05)。UH组血清、肺组织MPO活性及肺组织MDA含量均低于I组(P<0.05),与C组比较差异无统计学意义(P>0.05)。UH组IL-1β和TNF-αmRNA表达均低于I组(P<0.05),UH、UM、UL组IL-1βmRNA表达低于I组(P<0.05),与C组比较无显著差异(P>0.05),各组间TLR-4 mRNA表达水平比较,其差异均无统计学意义(P>0.05)。病理观察可见UTI用药组大鼠肺泡腔渗出及炎症细胞浸润程度均较I组减轻。结论 UTI可通过抗炎、抗氧化对黑火药烟雾所致大鼠肺损伤发挥保护作用,高剂量UTI可有效抑制IL-1β、TNF-αmRNA的表达。Objectives To explore the protective effect of ulinastatin （UTI） on inhalation lung injury caused by black gunpowder smoke in rats and its inhibitory effect on the mRNA expression of interleukin-1β （IL-1β） and tumor necrosis factor- （TNF-a）. Methods Thirty healthy male Wistar rats were randomly divided into 5 groups （n=6）： normal control group （C）, inhalation lung injury group （I）, high-dose UTI group （UH）, medium-dose UTI group （UM） and low-dose UTI group （UL）. The rat model of inhalation lung injury was reproduced by a self-made smoke generator. Rats in UH, UM and UL group were given 100000, 50000 and 20 000U/（kg.d）, respectively, of UTI by intraperitoneal injection. The animals were sacrificed 40h later, then the arterial blood gas values, lung wet-to-dry weight ratio （W/D）, white blood cell count and protein concentration in bronchoalveolar lavage fluid （BALF）, myeloperoxidase （MPO） activity in serum and lung tissue, and malondialdehyde （MDA） content in lung tissue were determined, and the macroscopic and histological changes in lung tissue were evaluated. The mRNA expression of toll-like receptor 4 （TLR-4）, IL-1βandTNF-e~ were determined by quantitative real-time reverse transcription-PCR （qRT-PCR）. Results The values of PaO2 in UH, UM and UL group were higher than that in group I （P〈0.05）, while W/D and WBC count in BALF were lower than those in group I （P〈0.05）. The protein concentration in BALF of UM and UL group was lower than that in group I （P〈0.05）. The PaOz, PaCO2, and W/D and protein concentration in BALF in UH, UM and UL group were similar to those in group C （P〉0.05）. MPO activity in serum and lung tissue and MDA content in UH group were both lower than those in group I （P〈0.05）, while they were similar to those in group C （P〉0.05）. qhe mRNA expression of TNF-ct in UH group was lower than that in group I, the mRNA expression of IL-1β in UH, UM and UL group was lower than that in group I （P�

关 键 词：乌司他丁 黑火药 烟雾吸入性肺损伤 白细胞介素1Β 肿瘤坏死因子A 

分 类 号：R563.9[医药卫生—呼吸系统]