高压氧联合ω-3多不饱和脂肪酸对急性肺损伤大鼠TLR4/NF-κB信号通路的影响  

Effects of hyperbaric oxygenation combined with ω-3 polyunsaturated fatty acid on TLR4/NF-κB signal pathway in the rats with acute lung injury

作　　者：芦玲 白琳[1] 兰玉怀[1] 武猛[1] 丛沛然 郝鑫 张琳[1] Lu Ling;Bai Lin;Lan Yuhuai;Wu Meng;Cong Peiran;Hao Xin;Zhang Lin(Department of Critical Care Medicine, Heilongjiang Hospital, Harbin 150036, China)

机构地区：[1]黑龙江省医院重症医学科,哈尔滨150036

出　　处：《中华航海医学与高气压医学杂志》2019年第4期303-306,共4页Chinese Journal of Nautical Medicine and Hyperbaric Medicine

基　　金：黑龙江省青年科学基金资助项目(QC2016127).

摘　　要：目的探讨高压氧(HBO)联合ω-3多不饱和脂肪酸(PUFAω-3)对脂多糖(LPS)诱导的急性肺损伤大鼠的保护作用及其机制.方法 48只SD大鼠按照数字表法随机分为对照组、模型组、实验组及联合组,每组12只.除对照组外,其余大鼠均采用LPS气管滴注法建立大鼠ALI模型,实验组灌胃给予PUFA ω-3(150 mg/kg),联合组在给予PUFA ω-3的基础上予以HBO治疗,对照组与模型组给予等体积蒸馏水,共给药14 d.末次给药后,取大鼠肺组织计算湿/干比,采用ELISA试剂盒检测肺组织匀浆液炎症因子TNF-α、IL-1β的含量,HE染色观察肺组织病理损伤情况,Western blotting实验检测肺组织中TLR4、NF-κB蛋白的表达情况.结果与对照组比较,模型组大鼠肺组织水肿明显,肺组织湿/干比显著增加(5.57±0.37 vs.4.16 ±0.19)(P<0.05);与模型组比较,实验组和联合组肺组织湿/干比下降(4.78±0.25,4.42±0.18 vs.5.57±0.37)(P<0.01或P<0.05),且联合组明显低于实验组(4.42±0.18 vs.4.78±0.25)(P<0.05).与对照组比较,模型组大鼠肺组织炎症因子TNF-α、IL-1β含量均显著增加(P<0.01或P<0.05);经PUFAω-3单独或联合HBO治疗后,与模型组比较,实验组和联合组大鼠肺组织中的TNF-α、IL-1β含量均明显下降(P<0.05),其中联合组下降更为明显(P<0.05).与对照组比较,模型组大鼠肺组织蛋白TLR4和NF-κB蛋白表达均显著上调(P<0.01);与模型组比较,实验组和联合组大鼠TLR4和NF-κB蛋白表达均下降(P<0.05或P<0.01),其中实验组对TLR4的调控作用更为明显(P<0.01);与实验组比较,联合组NF-κB表达下降更为明显(P<0.05).结论 HBO能增强PUFA ω-3对急性肺损伤大鼠肺组织的保护作用,降低炎症因子水平,其作用机制与调控TLR4/NF-κB信号通路有关.Objective To investigate the protective effect of hyperbaric oxygen (HBO) combined with ω-3 polyunsaturated fatty acid (PUFA ω-3) on lipopolysaccharide-induced acute lung injury in the rats and its related mechanism.Methods Forty-eight SD rats were randomly divided into the control group,the model group,the experimental group and the combined group,each consisting of 12 rats.With exception of the rats in the control group,acute lung injury (ALI) model was established by LPS tracheal instillation in the rats of the model and experimental groups.The experimental group received PUFA ω-3 (150 mg/kg) by gavage,the combined group was treated with HBO on the basis of PUFA omega-3,and equal volume of distilled water was given to the control and model groups.The course of treatment lasted for 14 days.After last medication,pulmonary tissues of the rats were collected and wet/dry ratio was calculated,and the inflammatory factors,TNF-α and IL-1β in the lung tissue homogenate were detected by ELISA test kit.HE staining was used to observe the pathological damage of the lung tissue,and the expression levels of TLR4 and NF-κB proteins in the lung tissue were detected by Western-blotting.Results Compared with the control group,pulmonary edema in the model group could clearly be seen,and the wet/dry ratio of the lung tissue increased markedly (5.57 ± 0.57 vs.4.16 ±0.19)(P <0.05).Compared with the model group,the wet/dry ratio of the lung tissue in the experimental and the combined groups decreased (4.78 ±0.25,4.42 ±0.18 vs.5.57 ±0.37)(P <0.01 or P < 0.05),and the wet/dry ratio of the combined group was obviously lower than that of the experimental group (4.42 ±0.18 vs.4.78 ±0.25)(P <0.05).As compared with the control group,the inflammatory factor levels of TNF-α and IL-1β in the model group all significantly increased(P < 0.01 or P < 0.05).Following treatment with simple PUFA ω-3 or coupled with HBO,the inflammatory factor levels of TNF-α and IL-1β in lung tissues of the experimental and the combined groups all

关 键 词：高压氧 Ω-3多不饱和脂肪酸 急性肺损伤 TLR4/NF-κB 

分 类 号：R563.8[医药卫生—呼吸系统]