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肿瘤坏死因子α诱导蛋白家族8样蛋白2在小鼠内毒素性急性肺损伤中的作用 被引量:2

Role of TIPE2 in endotoxin-induced acute lung injury in mice
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摘要 目的评价肿瘤坏死因子α诱导蛋白家族8样蛋白2(TIPE2)在小鼠内毒素性急性肺损伤(ALI)中的作用。方法SPF级健康成年雄性BALB/c小鼠40只,6~8周龄,体重20~25 g,采用随机数字表法分为4组(n=10):空载质粒组(VP组)、空载质粒组+ALI组(VP+ALI组)、腺相关病毒过表达TIPE2组(T组)和腺相关病毒过表达TIPE2组+ALI组(T+ALI组)。VP组和VP+ALI组气管内注射空载腺相关病毒,T组和T+ALI组气管内给予携带TIPE2干扰序列的腺相关病毒,3周后制备小鼠内毒素性ALI模型。VP组和T组气管内注射等容量PBS,VP+ALI组和T+ALI组气管内注射LPS 5 mg/kg。各组于注射LPS后24 h时采集腹主动脉血样,行血气分析并计算氧合指数(OI),采用ELISA法检测血清TNF-α浓度,随后处死小鼠取肺组织,HE染色观察病理学结果并行肺损伤评分,确定肺湿重/干重(W/D)比值,测定髓过氧化物酶(MPO)活性,采用Western blot法检测TIPE2、磷酸化c-Jun氨基末端激酶(p-JNK)和NF-κB的表达。结果与VP组比较,VP+ALI组肺损伤评分、W/D比值、MPO活性和血清TNF-α浓度升高,PaO2和OI降低,肺组织TIPE2表达下调,p-JNK和NF-κB表达上调(P<0.05),T组上述指标差异无统计学意义(P>0.05);与VP+ALI组比较,T+ALI组肺损伤评分、W/D比值、MPO活性和血清TNF-α浓度降低,PaO2和OI升高,肺组织TIPE2表达上调,p-JNK和NF-κB表达下调(P<0.05)。结论TIPE2表达下调参与了小鼠内毒素性ALI的过程。 Objective To evaluate the role of tumour necrosis factor-α-induced protein 8-like 2(TIPE2)in the acute lung injury(ALI)induced by endotoxin in mice.Methods Forty SPF healthy adult male BALB/c mice,aged 6-8 weeks,weighing 20-25 g,were divided into 4 groups(n=10 each)using a random number table method:vehicle plasmid group(VP group),vehicle plasmid plus ALI group(VP+ALI group),TIPE2 adeno-associated virus overexpression group(T group)and TIPE2 adeno-associated virus overexpression plus ALI group(T+ALI group).The mice in VP and VP+ALI groups were injected with empty adeno-associated virus,while the mice in T and T+ALI groups were intratracheally given adeno-associated virus carrying TIPE interference sequence.Three weeks later,the model of endotoxin-induced ALI was established.Lipopolysaccharide(LPS)5 mg/kg was intratracheally given in VP+ALI and T+ALI groups,and the equal volume of phosphate buffered saline(PBS)was given in VP and T groups.Blood samples were obtained from the abdominal aorta at 24 h after injection of LPS for blood gas analysis,oxygenation index(OI)was calculated,and tumor necrosis factor-alpha(TNF-α)in serum were detected by enzyme-linked immunosorbent assay.The animals were then sacrificed,and lung tissues were removed for examination of pathological changes which were scored after haematoxylin and eosin staining,for calculation of the wet/dry weight ratio(W/D ratio)and for determination of myeloperoxidase(MPO)activity and the expression of TIPE2,phosphorylated c-Jun N-terminal kinase(p-JNK)and nuclear factor kappa B(NF-κB)(by Western blot).Results Compared with VP group,the lung injury score,W/D ratio,MPO activity and concentration of serum TNF-αwere significantly increased,PaO2 and OI were decreased,expression of TIPE2 was down-regulated and expression of p-JNK and NF-κB was up-regulated in VP+ALI group(P<0.05).Compared with VP+ALI group,the lung injury score,W/D ratio,MPO activity and concentration of serum TNF-αwere significantly decreased,PaO2 and OI were increased,expression of TIPE2 was up-regulated and expression of p-JNK and NF-κB was down-regulated in T+ALI group(P<0.05).Conclusion The down-regulation of TIPE2 expression is involved in the process of ALI induced by endotoxin in mice.
作者 黄婷 孔倩 袁敏 何旋 陈鹤翔 明婷倩 王倩 吴晓静 Huang Ting;Kong Qian;Yuan Min;He Xuan;Chen Hexiang;Ming Tingqian;Wang Qian;Wu Xiaojing(Department of Anesthesiology,Renmin Hospital,Wuhan University,Wuhan 430060,China)
出处 《中华麻醉学杂志》 CAS CSCD 北大核心 2021年第4期478-481,共4页 Chinese Journal of Anesthesiology
基金 国家自然科学基金 (81901952) 湖北省自然科学基金 (2019CFB473,2020CFB222)。
关键词 泛素特异性蛋白酶类 脂多糖类 急性肺损伤 Ubiquitin-specific proteases Lipopolysaccharides Acute lung injury
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  • 1Zambon M, Vincent JL. Mortality rates for patients with acute lung injury/ARDS have decreased over time [J]. Chest, 2008, 133 (5): 1120-1127. DOI: 10.1378/chest.07-2134.
  • 2Bernard GR, Artigas A, Brigham KL, et al. The American- European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination [J]. Am J Respir Crit Care Med, 1994, 149 (3 Pt 1): 818-824. DOI: 10.1164/ajrccm. 149.3.7509706.
  • 3Freundt EC, Bidere N, Lenardo MJ. A different TIPE of immune homeostasis [J]. Cell, 2008, 133 (3): 401-402. DOI: 10.1016/j.cell. 2008.04.017.
  • 4Zhang X, Wang J, Fan C, et al. Crystal structure of TIPE2 provides insights into immune homeostasis [J]. Nat Struct Mol Biol, 2009, 16 (1): 89-90. DOI: 10.1038/nsmb.1522.
  • 5Ranieri VM, Rubenfeld GD, Thompson BT, et al. Acute respiratory distress syndrome: the Berlin Definition [J]. JAMA, 2012, 307 (23): 2526-2533. DOI: 10.1001/jama.2012.5669.
  • 6Sun H, Gong S, Carmody RJ, et al. TIPE2, a negative regulator of innate and adaptive immunity that maintains immune homeostasis [J].Cell, 2008, 133 (3): 415-426. DOI: 10.lO16/j.eell.2008.03.026.
  • 7Kumar H, Kawai T, Akira S. Pathogen recognition in the innate immune response [J]. Biochem J, 2009, 420 (1): 1-16. DOI: 10.1042/BJ20090272.
  • 8Randall RE, Goodbourn S. Interferons and viruses: an interplay between induction, signalling, antiviral responses and virus countermeasures [J]. J Gen Virol, 2008, 89 (Pt 1): 1-47. DOh 10.1099/vir.0.83391-0.
  • 9Samuel CE. Antiviral actions of interferons [J]. Clin Microbiol Rev, 2001, 14 (4): 778-809, table of contents. DOI: 10.1128/CMR. 14.4.778-809.2001.
  • 10Decker T, Miiller M, Stockinger S. The yin and yang of type | interferon activity in bacterial infection [J]. Nat Rev Immunol, 2005, 5 (9): 675-687. DOh 10.1038/nri1684.

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