脂多糖诱导大鼠吸入性肺炎动物模型的建立
|
摘要
目的建立脂多糖(LPS)诱导的大鼠吸入性肺炎动物模型。方法随机将48只3月龄清洁级雄性SD大鼠分为对照组和实验组(LPS组),LPS组大鼠采用气管内注射剂量为2 mg/kg脂多糖,对照组大鼠注射等量生理盐水,分别在注射LPS后6 h、1 d、3 d、5 d摘取大鼠眼球取血,采用ELISA法检测血清中炎性因子IL-6水平;应用HE染色观察大鼠肺脏病理学形态变化。结果 6 h后LPS组大鼠血清IL-6含量高于对照组(F=1.078,P<0.01)。HE染色后,可见LPS组大鼠出现肺组织结构毁损、肺间质大量中性粒细胞浸润、血管内皮细胞增生等病理变化。肺组织病理半定量评分提示LPS大鼠肺损伤以5d损伤最为明显。结论向大鼠气管内注射剂量为2 mg/kg的LPS可成功复制大鼠吸入性肺炎模型。
Objective To establish a rat model of aspiration pneumonia caused by airway lipopolysaccharide(LPS) inhalation. Methods Forty-eight clean grade male SD rats were randomly divided into control group and experimental group(LPS group).The rats in the LPS group were made aspiration pneumonia model by intratracheal injection of 2 mg/kg LPS, and the rats in the control group were treated the same amount of saline intervention.The rats were randomly assigned to four subgroups(n=6) to be sacrificed at 6 hours and 1,3,5 days after intratracheal injection.Expressions of interleukin-6 in lung tissue were detected by immunohistochemistry method,and the pathology morphology was observed by light microscope. Results the level of IL-6 in LPS group was significantly higher than that in control group at 6 hours(F=1.078,P<0.01).Light microscope showed that the lung tissue of LPS group was damaged,and the massive interstitial neutrophil infiltration and vascular endothelial cell proliferation as the main manifestation of pathology Change.the Lung histopathology semi-quantitative score showed that the lungs were the most severely damaged at fifth day. Conclusions A rat model of aspiration pneumonia could be established by intratracheal injection of LPS at a concentration of 2 mg/kg.
Objective To establish a rat model of aspiration pneumonia caused by airway lipopolysaccharide(LPS) inhalation. Methods Forty-eight clean grade male SD rats were randomly divided into control group and experimental group(LPS group).The rats in the LPS group were made aspiration pneumonia model by intratracheal injection of 2 mg/kg LPS, and the rats in the control group were treated the same amount of saline intervention.The rats were randomly assigned to four subgroups(n=6) to be sacrificed at 6 hours and 1,3,5 days after intratracheal injection.Expressions of interleukin-6 in lung tissue were detected by immunohistochemistry method,and the pathology morphology was observed by light microscope. Results the level of IL-6 in LPS group was significantly higher than that in control group at 6 hours(F=1.078,P<0.01).Light microscope showed that the lung tissue of LPS group was damaged,and the massive interstitial neutrophil infiltration and vascular endothelial cell proliferation as the main manifestation of pathology Change.the Lung histopathology semi-quantitative score showed that the lungs were the most severely damaged at fifth day. Conclusions A rat model of aspiration pneumonia could be established by intratracheal injection of LPS at a concentration of 2 mg/kg.
引文
[1] Lanspa MJ,Peyrani P,Wiemken T,et al.Characteristics associated with clinician diagnosis of aspiration pneumonia:a descriptive study of afflicted patients and their outcomes[J].J Hosp Med,2015,10(2):90-96.
[2] Kapoor K,Singla E,Sahu B,et al.PARP inhibitor,olaparib ameliorates acute lung and kidney injury upon intratracheal administration of LPS in mice[J].Mol Cell Biochem,2015,400(1-2):153-162.
[3] Xu XP,Huang LL,Hu SL,et al.Genetic modification of mesenchymal stem cells overexpressing angiotensin Ⅱ type 2 receptor increases cell migration to injured lung in LPS-induced acute lung injury mice[J].Stem Cells Transl Med,2018,7(10):721-730.
[4] 罗友,吴欣瞳,庞欣欣,等.小鼠急性肺损伤造模条件的探究[J].中国畜牧兽医,2017,44(8):2269-2276.
[5] 马文东,袁媛,杨奕,等.TGF-β1介导的RhoA/ROCK通路在大鼠肺肌成纤维细胞分化中的调节作用[J].中国病理生理杂志,2013,29(10):1758-1763.
[6] 梁颖红,龚艳杰,刘佳,等.输血相关急性肺损伤大鼠肺组织细胞因子诱导的中性粒细胞趋化因子的表达.中国呼吸与危重监护杂志,2016,15(4):379-383.
[7] 袁伟锋,李理,徐虹,等.气管内滴入与腹膜腔注射脂多糖致肺组织炎症损伤的动态变化比较[J].中国呼吸与危重监护杂志,2017,16(3):274-279.
[8] Mikawa K,Nishina K,Takao Y,et al.ONO-1714,a nitric oxide synthase inhibitor,attenuates endotoxin-induced acute lung injury in rabbits[J].Anesth Analg,2003,97(6):1751-1755.
[9] 刘慧珍,赵国伟,高钧.脑卒中合并肺部感染患者病原体分布及抗生素应用研究[J/OL].中国预防医学杂志,2017,18(10):793-795.
[10] Teh WH,Smith CJ,Barlas RS,et al.Impact of stroke-associated pneumonia on mortality,length of hospitalization,and functional outcome[J].Acta Neurol Scand,2018,138(4):293-300.
[11] 孙敏敏.老年脑卒中合并吸入性肺炎临床特征观察[J].临床肺科杂志,2017,22(1):168-170.
[12] Mou Y,Jian YL,Chen T,et al.Synthesis and evaluation of 2-cyano-3,12-dioxooleana-1,9(11)-en-28-oate-13β,28-olide as a potent anti-inflammatory agent for intervention of LPS-induced acute lung injury[J].Chin J Nat Med,2017,15(5):347-354.
[13] 李懿,侯旭阳,吴益蓉,等.Caveolin-1/MCP-1/IL-12在LPS诱导的急性肺损伤模型中的作用[J].湖南师范大学学报(医学版),2018,15(2):9-13.
[14] D′Almeida APL,Pacheco de Oliveira MT,de Souza éT,et al.α-bisabolol-loaded lipid-core nanocapsules reduce lipopolysaccharide-induced pulmonary inflammation in mice[J].Int J Nanomedicine,2017,12:4479-4491.
[15] Andrijevic I,Matijasevic J,Andrijevic L,et al.Interleukin-6 and procalcitonin as biomarkers in mortality prediction of hospitalized patients with community acquired pneumonia[J].Ann Thorac Med,2014,9(3):162-167.
[16] 高延秋,张华,刘敏,等.重症肺炎患者外周血IL-6和IL-18水平的检测[J].郑州大学学报(医学版),2015,50(4):555-558.
[2] Kapoor K,Singla E,Sahu B,et al.PARP inhibitor,olaparib ameliorates acute lung and kidney injury upon intratracheal administration of LPS in mice[J].Mol Cell Biochem,2015,400(1-2):153-162.
[3] Xu XP,Huang LL,Hu SL,et al.Genetic modification of mesenchymal stem cells overexpressing angiotensin Ⅱ type 2 receptor increases cell migration to injured lung in LPS-induced acute lung injury mice[J].Stem Cells Transl Med,2018,7(10):721-730.
[4] 罗友,吴欣瞳,庞欣欣,等.小鼠急性肺损伤造模条件的探究[J].中国畜牧兽医,2017,44(8):2269-2276.
[5] 马文东,袁媛,杨奕,等.TGF-β1介导的RhoA/ROCK通路在大鼠肺肌成纤维细胞分化中的调节作用[J].中国病理生理杂志,2013,29(10):1758-1763.
[6] 梁颖红,龚艳杰,刘佳,等.输血相关急性肺损伤大鼠肺组织细胞因子诱导的中性粒细胞趋化因子的表达.中国呼吸与危重监护杂志,2016,15(4):379-383.
[7] 袁伟锋,李理,徐虹,等.气管内滴入与腹膜腔注射脂多糖致肺组织炎症损伤的动态变化比较[J].中国呼吸与危重监护杂志,2017,16(3):274-279.
[8] Mikawa K,Nishina K,Takao Y,et al.ONO-1714,a nitric oxide synthase inhibitor,attenuates endotoxin-induced acute lung injury in rabbits[J].Anesth Analg,2003,97(6):1751-1755.
[9] 刘慧珍,赵国伟,高钧.脑卒中合并肺部感染患者病原体分布及抗生素应用研究[J/OL].中国预防医学杂志,2017,18(10):793-795.
[10] Teh WH,Smith CJ,Barlas RS,et al.Impact of stroke-associated pneumonia on mortality,length of hospitalization,and functional outcome[J].Acta Neurol Scand,2018,138(4):293-300.
[11] 孙敏敏.老年脑卒中合并吸入性肺炎临床特征观察[J].临床肺科杂志,2017,22(1):168-170.
[12] Mou Y,Jian YL,Chen T,et al.Synthesis and evaluation of 2-cyano-3,12-dioxooleana-1,9(11)-en-28-oate-13β,28-olide as a potent anti-inflammatory agent for intervention of LPS-induced acute lung injury[J].Chin J Nat Med,2017,15(5):347-354.
[13] 李懿,侯旭阳,吴益蓉,等.Caveolin-1/MCP-1/IL-12在LPS诱导的急性肺损伤模型中的作用[J].湖南师范大学学报(医学版),2018,15(2):9-13.
[14] D′Almeida APL,Pacheco de Oliveira MT,de Souza éT,et al.α-bisabolol-loaded lipid-core nanocapsules reduce lipopolysaccharide-induced pulmonary inflammation in mice[J].Int J Nanomedicine,2017,12:4479-4491.
[15] Andrijevic I,Matijasevic J,Andrijevic L,et al.Interleukin-6 and procalcitonin as biomarkers in mortality prediction of hospitalized patients with community acquired pneumonia[J].Ann Thorac Med,2014,9(3):162-167.
[16] 高延秋,张华,刘敏,等.重症肺炎患者外周血IL-6和IL-18水平的检测[J].郑州大学学报(医学版),2015,50(4):555-558.